Recommendation on Design, Execution, and Reporting of Animal Atherosclerosis Studies: A Scientific Statement from the American Heart Association

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 37, Issue 9, 2017, Pages e131-e157

  Daugherty, Alan ^a   Tall, Alan R ^b   Daemen, Mat J A P ^c   Falk, Erling ^d   Fisher, Edward A ^e   García Cardeña, Guillermo ^f   Lusis, Aldons J ^g   Owens, A Phillip ^h   Rosenfeld, Michael E ⁱ   Virmani, Renu ^j  

^a UNIVERSITY OF KENTUCKY   (United States)

^b Columbia University Medicine ^*  (United States)

^c ACADEMIC MEDICAL CENTER   (Netherlands)

^d AARHUS UNIVERSITY HOSPITAL   (Denmark)

^e NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f BRIGHAM AND WOMEN S HOSPITAL   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

^h UNIVERSITY OF CINCINNATI   (United States)

ⁱ UNIVERSITY OF WASHINGTON   (United States)

^j CVPATH INSTITUTE   (United States)

more..

Author keywords

AHA Scientific Statements; animal models; atherosclerosis; cholesterol; histology; pathology

Indexed keywords

CHOLESTEROL; LIPOPROTEIN;

ARTICLE; ATHEROSCLEROSIS; COMORBIDITY; DIABETES MELLITUS; EXPERIMENTAL DESIGN; HUMAN; HYPERTENSION; IMMUNOHISTOCHEMISTRY; KIDNEY FAILURE; LEPORIDAE; MEASUREMENT ACCURACY; MEDICAL SOCIETY; NONHUMAN; OBESITY; OUTCOME ASSESSMENT; PIG; PRACTICE GUIDELINE; PRIORITY JOURNAL; ANIMAL; DISEASE MODEL; GENETICS; INFORMATION PROCESSING; MEDICAL RESEARCH; METABOLISM; METHODOLOGY; MOUSE; PATHOLOGY; PATHOPHYSIOLOGY; PRIMATE; SPECIES DIFFERENCE; STANDARDS; TRANSGENIC MOUSE; UNITED STATES;

AMERICAN HEART ASSOCIATION; ANIMALS; ATHEROSCLEROSIS; BIOMEDICAL RESEARCH; DATA COLLECTION; DISEASE MODELS, ANIMAL; HUMANS; MICE; MICE, TRANSGENIC; PRIMATES; RABBITS; RESEARCH DESIGN; SPECIES SPECIFICITY; SWINE; UNITED STATES;

EID: 85025443586     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATV.0000000000000062     Document Type: Article

References (249)

1. Enos WF, Holmes RH, Beyer J. Coronary disease among United States soldiers killed in action in Korea: preliminary report. J Am Med Assoc. 1953;152:1090-1093.
2. McNamara JJ, Molot MA, Stremple JF, Cutting RT. Coronary artery disease in combat casualties in Vietnam. JAMA. 1971;216:1185-1187.
3. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Natural history of aortic and coronary atherosclerotic lesions in youth: findings from the PDAY Study. Arterioscler Thromb. 1993;13:1291-1298.
4. Stary HC, Blankenhorn DH, Chandler AB, Glagov S, Insull W Jr, Richardson M, Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD. A definition of the intima of human arteries and of its atherosclerosis-prone regions: a report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb. 1992;12:120-134.
5. Stary HC, Chandler AB, Glagov S, Guyton JR, Insull W Jr, Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD, Wissler RW. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis: a report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb. 1994;14:840-856.
6. Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W Jr, Rosenfeld ME, Schwartz CJ, Wagner WD, Wissler RW. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis: a report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb Vasc Biol. 1995;15:1512-1531.
7. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000;20:1262-1275.
8. Jarinova O, Stewart AF, Roberts R, Wells G, Lau P, Naing T, Buerki C, McLean BW, Cook RC, Parker JS, McPherson R. Functional analysis of the chromosome 9p21.3 coronary artery disease risk locus. Arterioscler Thromb Vasc Biol. 2009;29:1671-1677. doi: 10.1161/ATVBAHA.109.189522.
9. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447:661-678.
10. Steinberg D. In celebration of the 100th anniversary of the lipid hypothesis of atherosclerosis. J Lipid Res. 2013;54:2946-2949. doi: 10.1194/jlr. R043414.
11. Hegele RA, Gidding SS, Ginsberg HN, McPherson R, Raal FJ, Rader DJ, Robinson JG, Welty FK. Nonstatin low-density lipoprotein-lowering therapy and cardiovascular risk reduction: statement from ATVB Council. Arterioscler Thromb Vasc Biol. 2015;35:2269-2280. doi: 10.1161/ ATVBAHA.115.306442.
12. Pasterkamp G, van der Laan SW, Haitjema S, Foroughi Asl H, Siemelink MA, Bezemer T, van Setten J, Dichgans M, Malik R, Worrall BB, Schunkert H, Samani NJ, de Kleijn DP, Markus HS, Hoefer IE, Michoel T, de Jager SC, Björkegren JL, den Ruijter HM, Asselbergs FW. Human validation of genes associated with a murine atherosclerotic phenotype. Arterioscler Thromb Vasc Biol. 2016;36:1240-1246. doi: 10.1161/ ATVBAHA.115.306958.
13. von Scheidt M, Zhao Y, Kurt Z, Pan C, Zeng L, Yang X, Schunkert H, Lusis AJ. Applications and limitations of mouse models for understanding human atherosclerosis. Cell Metab. 2017;25:248-261. doi: 10.1016/j. cmet.2016.11.001.
14. Masucci-Magoulas L, Goldberg IJ, Bisgaier CL, Serajuddin H, Francone OL, Breslow JL, Tall AR. A mouse model with features of familial combined hyperlipidemia. Science. 1997;275:391-394.
15. Pennacchio LA, Olivier M, Hubacek JA, Cohen JC, Cox DR, Fruchart JC, Krauss RM, Rubin EM. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science. 2001;294:169-173. doi: 10.1126/science.1064852.
16. Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, Beckmann JS, Bragg-Gresham JL, Chang HY, Demirkan A, Den Hertog HM, Donnelly LA, Ehret GB, Esko T, Feitosa MF, Ferreira T, Fischer K, Fontanillas P, Fraser RM, Freitag DF, Gurdasani D, Heikkilä K, Hyppönen E, Isaacs A, Jackson AU, Johansson A, Johnson T, Kaakinen M, Kettunen J, Kleber ME, Li X, Luan J, Lyytikäinen LP, Magnusson PK, Mangino M, Mihailov E, Montasser ME, Müller-Nurasyid M, Nolte IM, O'Connell JR, Palmer CD, Perola M, Petersen AK, Sanna S, Saxena R, Service SK, Shah S, Shungin D, Sidore C, Song C, Strawbridge RJ, Surakka I, Tanaka T, Teslovich TM, Thorleifsson G, Van den Herik EG, Voight BF, Volcik KA, Waite LL, Wong A, Wu Y, Zhang W, Absher D, Asiki G, Barroso I, Been LF, Bolton JL, Bonnycastle LL, Brambilla P, Burnett MS, Cesana G, Dimitriou M, Doney AS, Döring A, Elliott P, Epstein SE, Eyjolfsson GI, Gigante B, Goodarzi MO, Grallert H, Gravito ML, Groves CJ, Hallmans G, Hartikainen AL, Hayward C, Hernandez D, Hicks AA, Holm H, Hung YJ, Illig T, Jones MR, Kaleebu P, Kastelein JJ, Khaw KT, Kim E, Klopp N, Komulainen P, Kumari M, Langenberg C, Lehtimäki T, Lin SY, Lindström J, Loos RJ, Mach F, McArdle WL, Meisinger C, Mitchell BD, Müller G, Nagaraja R, Narisu N, Nieminen TV, Nsubuga RN, Olafsson I, Ong KK, Palotie A, Papamarkou T, Pomilla C, Pouta A, Rader DJ, Reilly MP, Ridker PM, Rivadeneira F, Rudan I, Ruokonen A, Samani N, Scharnagl H, Seeley J, Silander K, Stančáková A, Stirrups K, Swift AJ, Tiret L, Uitterlinden AG, van Pelt LJ, Vedantam S, Wainwright N, Wijmenga C, Wild SH, Willemsen G, Wilsgaard T, Wilson JF, Young EH, Zhao JH, Adair LS, Arveiler D, Assimes TL, Bandinelli S, Bennett F, Bochud M, Boehm BO, Boomsma DI, Borecki IB, Bornstein SR, Bovet P, Burnier M, Campbell H, Chakravarti A, Chambers JC, Chen YD, Collins FS, Cooper RS, Danesh J, Dedoussis G, de Faire U, Feranil AB, Ferrières J, Ferrucci L, Freimer NB, Gieger C, Groop LC, Gudnason V, Gyllensten U, Hamsten A, Harris TB, Hingorani A, Hirschhorn JN, Hofman A, Hovingh GK, Hsiung CA, Humphries SE, Hunt SC, Hveem K, Iribarren C, Järvelin MR, Jula A, Kähönen M, Kaprio J, Kesäniemi A, Kivimaki M, Kooner JS, Koudstaal PJ, Krauss RM, Kuh D, Kuusisto J, Kyvik KO, Laakso M, Lakka TA, Lind L, Lindgren CM, Martin NG, März W, McCarthy MI, McKenzie CA, Meneton P, Metspalu A, Moilanen L, Morris AD, Munroe PB, Njølstad I, Pedersen NL, Power C, Pramstaller PP, Price JF, Psaty BM, Quertermous T, Rauramaa R, Saleheen D, Salomaa V, Sanghera DK, Saramies J, Schwarz PE, Sheu WH, Shuldiner AR, Siegbahn A, Spector TD, Stefansson K, Strachan DP, Tayo BO, Tremoli E, Tuomilehto J, Uusitupa M, van Duijn CM, Vollenweider P, Wallentin L, Wareham NJ, Whitfield JB, Wolffenbuttel BH, Altshuler D, Ordovas JM, Boerwinkle E, Palmer CN, Thorsteinsdottir U, Chasman DI, Rotter JI, Franks PW, Ripatti S, Cupples LA, Sandhu MS, Rich SS, Boehnke M, Deloukas P, Mohlke KL, Ingelsson E, Abecasis GR, Daly MJ, Neale BM, Kathiresan S. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet. 2013;45:1345-1352. doi: 10.1038/ng.2795.
17. TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute, Crosby J, Peloso GM, Auer PL, Crosslin DR, Stitziel NO, Lange LA, Lu Y, Tang ZZ, Zhang H, Hindy G, Masca N, Stirrups K, Kanoni S, Do R, Jun G, Hu Y, Kang HM, Xue C, Goel A, Farrall M, Duga S, Merlini PA, Asselta R, Girelli D, Olivieri O, Martinelli N, Yin W, Reilly D, Speliotes E, Fox CS, Hveem K, Holmen OL, Nikpay M, Farlow DN, Assimes TL, Franceschini N, Robinson J, North KE, Martin LW, DePristo M, Gupta N, Escher SA, Jansson JH, Van Zuydam N, Palmer CN, Wareham N, Koch W, Meitinger T, Peters A, Lieb W, Erbel R, Konig IR, Kruppa J, Degenhardt F, Gottesman O, Bottinger EP, O'Donnell CJ, Psaty BM, Ballantyne CM, Abecasis G, Ordovas JM, Melander O, Watkins H, Orho-Melander M, Ardissino D, Loos RJ, McPherson R, Willer CJ, Erdmann J, Hall AS, Samani NJ, Deloukas P, Schunkert H, Wilson JG, Kooperberg C, Rich SS, Tracy RP, Lin DY, Altshuler D, Gabriel S, Nickerson DA, Jarvik GP, Cupples LA, Reiner AP, Boerwinkle E, Kathiresan S. Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med. 2014;371:22-31.
18. Rubin EM, Krauss RM, Spangler EA, Verstuyft JG, Clift SM. Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI. Nature. 1991;353:265-267. doi: 10.1038/353265a0.
19. Plump AS, Scott CJ, Breslow JL. Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci U S A. 1994;91:9607-9611.
20. Gibson CM, Korjian S, Tricoci P, Daaboul Y, Alexander JH, Steg PG, Lincoff AM, Kastelein JJ, Mehran R, D'Andrea D, Merkely B, Zarebinski M, Ophius TO, Harrington RA. Rationale and design of Apo-I Event Reduction in Ischemic Syndromes I (AEGIS-I): a phase 2b, randomized, placebo-controlled, dose-ranging trial to investigate the safety and tolerability of CSL112, a reconstituted, infusible, human apoA-I, after acute myocardial infarction. Am Heart J. 2016;180:22-28. doi: 10.1016/j. ahj.2016.06.017.
21. Maxwell KN, Fisher EA, Breslow JL. Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc Natl Acad Sci U S A. 2005;102:2069-2074. doi: 10.1073/ pnas.0409736102.
22. Lagace TA, Curtis DE, Garuti R, McNutt MC, Park SW, Prather HB, Anderson NN, Ho YK, Hammer RE, Horton JD. Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest. 2006;116:2995-3005. doi: 10.1172/ JCI29383.
23. Kastelein JJ, Ginsberg HN, Langslet G, Hovingh GK, Ceska R, Dufour R, Blom D, Civeira F, Krempf M, Lorenzato C, Zhao J, Pordy R, Baccara-Dinet MT, Gipe DA, Geiger MJ, Farnier M. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015;36:2996-3003. doi: 10.1093/eurheartj/ehv370.
24. Bentzon JF, Falk E. Atherosclerotic lesions in mouse and man: is it the same disease? Curr Opin Lipidol. 2010;21:434-440. doi: 10.1097/ MOL.0b013e32833ded6a.
25. Libby P. Murine "model" monotheism: an iconoclast at the altar of mouse. Circ Res. 2015;117:921-925. doi: 10.1161/CIRCRESAHA.115.307523.
26. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145:341-355. doi: 10.1016/j.cell.2011.04.005.
27. Kume N, Cybulsky MI, Gimbrone MA Jr. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest. 1992;90:1138-1144. doi: 10.1172/JCI115932.
28. Ait-Oufella H, Taleb S, Mallat Z, Tedgui A. Recent advances on the role of cytokines in atherosclerosis. Arterioscler Thromb Vasc Biol. 2011;31:969-979. doi: 10.1161/ATVBAHA.110.207415.
29. Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12:204-212. doi: 10.1038/ni.2001.
30. Chou MY, Fogelstrand L, Hartvigsen K, Hansen LF, Woelkers D, Shaw PX, Choi J, Perkmann T, Bäckhed F, Miller YI, Hörkkö S, Corr M, Witztum JL, Binder CJ. Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans. J Clin Invest. 2009;119:1335-1349. doi: 10.1172/JCI36800.
31. Otsuka F, Sakakura K, Yahagi K, Joner M, Virmani R. Has our understanding of calcification in human coronary atherosclerosis progressed? [published correction appears in Arterioscler Thromb Vasc Biol. 2014;34:e17]. Arterioscler Thromb Vasc Biol. 2014;34:724-736. doi: 10.1161/ATVBAHA. 113.302642.
32. Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162:597-605. doi: 10.1016/j. ahj.2011.06.012.
33. Caligiuri G, Levy B, Pernow J, Thorén P, Hansson GK. Myocardial infarction mediated by endothelin receptor signaling in hypercholesterolemic mice. Proc Natl Acad Sci U S A. 1999;96:6920-6924.
34. Braun A, Trigatti BL, Post MJ, Sato K, Simons M, Edelberg JM, Rosenberg RD, Schrenzel M, Krieger M. Loss of SR-BI expression leads to the early onset of occlusive atherosclerotic coronary artery disease, spontaneous myocardial infarctions, severe cardiac dysfunction, and premature death in apolipoprotein E-deficient mice. Circ Res. 2002;90:270-276.
35. Getz GS, Reardon CA. Do the Apoe-/- and Ldlr-/- mice yield the same insight on atherogenesis? Arterioscler Thromb Vasc Biol. 2016;36:1734-1741. doi: 10.1161/ATVBAHA.116.306874.
36. Zhang SH, Reddick RL, Piedrahita JA, Maeda N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science. 1992;258:468-471.
37. Plump AS, Smith JD, Hayek T, Aalto-Setälä K, Walsh A, Verstuyft JG, Rubin EM, Breslow JL. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell. 1992;71:343-353.
38. Nakashima Y, Plump AS, Raines EW, Breslow JL, Ross R. ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb. 1994;14:133-140.
39. Dansky HM, Charlton SA, Harper MM, Smith JD. T and B lymphocytes play a minor role in atherosclerotic plaque formation in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci U S A. 1997;94:4642-4646.
40. Getz GS, Reardon CA. Apoprotein E as a lipid transport and signaling protein in the blood, liver, and artery wall. J Lipid Res. 2009;50(suppl):S156-S161. doi: 10.1194/jlr.R800058-JLR200.
41. Linton MF, Atkinson JB, Fazio S. Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation. Science. 1995;267:1034-1037.
42. Boisvert WA, Spangenberg J, Curtiss LK. Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by bone marrow transplantation. J Clin Invest. 1995;96:1118-1124. doi: 10.1172/ JCI118098.
43. Ishibashi S, Goldstein JL, Brown MS, Herz J, Burns DK. Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. J Clin Invest. 1994;93:1885-1893. doi: 10.1172/ JCI117179.
44. Merat S, Fruebis J, Sutphin M, Silvestre M, Reaven PD. Effect of aging on aortic expression of the vascular cell adhesion molecule-1 and atherosclerosis in murine models of atherosclerosis. J Gerontol A Biol Sci Med Sci. 2000;55:B85-B94.
45. Reddick RL, Zhang SH, Maeda N. Atherosclerosis in mice lacking apo E: evaluation of lesional development and progression [published correction appears in Arterioscler Thromb 1994;14:839]. Arterioscler Thromb. 1994;14:141-147.
46. Fazio S, Hasty AH, Carter KJ, Murray AB, Price JO, Linton MF. Leukocyte low density lipoprotein receptor (LDL-R) does not contribute to LDL clearance in vivo: bone marrow transplantation studies in the mouse. J Lipid Res. 1997;38:391-400.
47. Babaev VR, Ding L, Reese J, Morrow JD, Breyer MD, Dey SK, Fazio S, Linton MF. Cyclooxygenase-1 deficiency in bone marrow cells increases early atherosclerosis in apolipoprotein E-and low-density lipoprotein receptor-null mice. Circulation. 2006;113:108-117. doi: 10.1161/ CIRCULATIONAHA.105.591537.
48. Lu H, Rateri DL, Feldman DL, Charnigo RJ Jr, Fukamizu A, Ishida J, Oesterling EG, Cassis LA, Daugherty A. Renin inhibition reduces hypercholesterolemia-induced atherosclerosis in mice. J Clin Invest. 2008;118:984-993. doi: 10.1172/JCI32970.
49. Powell-Braxton L, Véniant M, Latvala RD, Hirano KI, Won WB, Ross J, Dybdal N, Zlot CH, Young SG, Davidson NO. A mouse model of human familial hypercholesterolemia: markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet [published correction appears in Nat Med 1998;4:1200]. Nat Med. 1998;4:934-938.
50. Véniant MM, Withycombe S, Young SG. Lipoprotein size and atherosclerosis susceptibility in Apoe-/- and Ldlr-/- mice. Arterioscler Thromb Vasc Biol. 2001;21:1567-1570.
51. Westerterp M, van der Hoogt CC, de Haan W, Offerman EH, Dallinga-Thie GM, Jukema JW, Havekes LM, Rensen PC. Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE∗3-Leiden mice. Arterioscler Thromb Vasc Biol. 2006;26:2552-2559. doi: 10.1161/01.ATV.0000243925.65265.3c.
52. Knouff C, Hinsdale ME, Mezdour H, Altenburg MK, Watanabe M, Quarfordt SH, Sullivan PM, Maeda N. Apo E structure determines VLDL clearance and atherosclerosis risk in mice. J Clin Invest. 1999;103:1579-1586. doi: 10.1172/JCI6172.
53. Libby P, Lichtman AH, Hansson GK. Immune effector mechanisms implicated in atherosclerosis: from mice to humans [published correction appears in Immunity. 2013;39:413]. Immunity. 2013;38:1092-1104. doi: 10.1016/j.immuni.2013.06.009.
54. Kirchgessner TG, Sleph P, Ostrowski J, Lupisella J, Ryan CS, Liu X, Fernando G, Grimm D, Shipkova P, Zhang R, Garcia R, Zhu J, He A, Malone H, Martin R, Behnia K, Wang Z, Barrett YC, Garmise RJ, Yuan L, Zhang J, Gandhi MD, Wastall P, Li T, Du S, Salvador L, Mohan R, Cantor GH, Kick E, Lee J, Frost RJ. Beneficial and adverse effects of an LXR agonist on human lipid and lipoprotein metabolism and circulating neutrophils. Cell Metab. 2016;24:223-233. doi: 10.1016/j.cmet.2016.07.016.
55. Brousseau ME, Hoeg JM. Transgenic rabbits as models for atherosclerosis research. J Lipid Res. 1999;40:365-375.
56. Castellani LW, Goto AM, Lusis AJ. Studies with apolipoprotein A-II transgenic mice indicate a role for HDLs in adiposity and insulin resistance. Diabetes. 2001;50:643-651.
57. Rosenfeld ME, Tsukada T, Chait A, Bierman EL, Gown AM, Ross R. Fatty streak expansion and maturation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis. 1987;7:24-34.
58. Rosenfeld ME, Tsukada T, Gown AM, Ross R. Fatty streak initiation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis. 1987;7:9-23.
59. Buja LM, Kita T, Goldstein JL, Watanabe Y, Brown MS. Cellular pathology of progressive atherosclerosis in the WHHL rabbit: an animal model of familial hypercholesterolemia. Arteriosclerosis. 1983;3:87-101.
60. Atkinson JB, Hoover RL, Berry KK, Swift LL. Cholesterol-fed heterozygous Watanabe heritable hyperlipidemic rabbits: a new model for atherosclerosis. Atherosclerosis. 1989;78:123-136.
61. Phelan JP, Van Lenten BJ, Fogelman AM, Kean C, Haberland ME, Edwards PA. Notes on the breeding of the WHHL rabbit: an animal model of familial hypercholesterolemia. J Lipid Res. 1985;26:776-778.
62. Harsch M, Gebhardt A, Reymann A, Lang G, Schliack M, Löser R, Braesen JH, Niendorf A. Effects of pravastatin on cholesterol metabolism of cholesterol-fed heterozygous WHHL rabbits. Br J Pharmacol. 1998;124:277-282. doi: 10.1038/sj.bjp.0701831.
63. Niimi M, Yang D, Kitajima S, Ning B, Wang C, Li S, Liu E, Zhang J, Eugene Chen Y, Fan J. ApoE knockout rabbits: a novel model for the study of human hyperlipidemia. Atherosclerosis. 2016;245:187-193. doi: 10.1016/j.atherosclerosis.2015.12.002.
64. McPherson R, Lau P, Kussie P, Barrett H, Tall AR. Plasma kinetics of cholesteryl ester transfer protein in the rabbit: effects of dietary cholesterol. Arterioscler Thromb Vasc Biol. 1997;17:203-210.
65. Barter PJ, Ha YC, Calvert GD. Studies of esterified cholesterol in sub-fractions of plasma high density lipoproteins. Atherosclerosis. 1981;38:165-175.
66. St Clair RW. Atherosclerosis regression in animal models: current concepts of cellular and biochemical mechanisms. Prog Cardiovasc Dis. 1983;26:109-132.
67. Gerrity RG, Richardson M, Somer JB, Bell FP, Schwartz CJ. Endothelial cell morphology in areas of in vivo Evans blue uptake in the aorta of young pigs, II: ultrastructure of the intima in areas of differing permeability to proteins. Am J Pathol. 1977;89:313-334.
68. Civelek M, Manduchi E, Riley RJ, Stoeckert CJ Jr, Davies PF. Coronary artery endothelial transcriptome in vivo: identification of endoplasmic reticulum stress and enhanced reactive oxygen species by gene connectivity network analysis. Circ Cardiovasc Genet. 2011;4:243-252. doi: 10.1161/CIRCGENETICS.110.958926.
69. Granada JF, Kaluza GL, Wilensky RL, Biedermann BC, Schwartz RS, Falk E. Porcine models of coronary atherosclerosis and vulnerable plaque for imaging and interventional research. EuroIntervention. 2009;5:140-148.
70. Chatzizisis YS, Jonas M, Coskun AU, Beigel R, Stone BV, Maynard C, Gerrity RG, Daley W, Rogers C, Edelman ER, Feldman CL, Stone PH. Prediction of the localization of high-risk coronary atherosclerotic plaques on the basis of low endothelial shear stress: an intravascular ultrasound and histopathology natural history study. Circulation. 2008;117:993-1002. doi: 10.1161/CIRCULATIONAHA.107.695254.
71. Prescott MF, McBride CH, Hasler-Rapacz J, Von Linden J, Rapacz J. Development of complex atherosclerotic lesions in pigs with inherited hyper-LDL cholesterolemia bearing mutant alleles for apolipoprotein B. Am J Pathol. 1991;139:139-147.
72. Gerrity RG, Natarajan R, Nadler JL, Kimsey T. Diabetes-induced accelerated atherosclerosis in swine. Diabetes. 2001;50:1654-1665.
73. Kragel AH, Roberts WC. Composition of atherosclerotic plaques in the coronary arteries in homozygous familial hypercholesterolemia. Am Heart J. 1991;121(Pt 1):210-211.
74. Al-Mashhadi RH, Sørensen CB, Kragh PM, Christoffersen C, Mortensen MB, Tolbod LP, Thim T, Du Y, Li J, Liu Y, Moldt B, Schmidt M, Vajta G, Larsen T, Purup S, Bolund L, Nielsen LB, Callesen H, Falk E, Mikkelsen JG, Bentzon JF. Familial hypercholesterolemia and atherosclerosis in cloned minipigs created by DNA transposition of a human PCSK9 gain-of-function mutant. Sci Transl Med. 2013;5:166ra1. doi: 10.1126/ scitranslmed.3004853.
75. Davis BT, Wang XJ, Rohret JA, Struzynski JT, Merricks EP, Bellinger DA, Rohret FA, Nichols TC, Rogers CS. Targeted disruption of LDLR causes hypercholesterolemia and atherosclerosis in Yucatan miniature pigs. PLoS One. 2014;9:e93457. doi: 10.1371/journal.pone.0093457.
76. Manalo-Estrella P, Cox GE, Taylor CB. Atherosclerosis in Rhesus monkeys, VII: mechanism of hypercholesteremia: hepatic cholesterolgenesis and the hypercholesteremic threshold of dietary cholesterol. Arch Pathol. 1963;76:413-423.
77. Clarkson TB, Prichard RW, Morgan TM, Petrick GS, Klein KP. Remodeling of coronary arteries in human and nonhuman primates. JAMA. 1994;271:289-294.
78. Portman OW, Andrus SB. Comparative evaluation of three species of new world monkeys for studies of dietary factors, tissue lipids, and atherogenesis. J Nutr. 1965;87:429-438.
79. Jokinen MP, Clarkson TB, Prichard RW. Animal models in atherosclerosis research. Exp Mol Pathol. 1985;42:1-28.
80. Clarkson TB, Weingand KW, Kaplan JR, Adams MR. Mechanisms of atherogenesis. Circulation. 1987;76(Pt 2):I20-I28.
81. Shively CA, Clarkson TB, Kaplan JR. Social deprivation and coronary artery atherosclerosis in female cynomolgus monkeys. Atherosclerosis. 1989;77:69-76.
82. Kaplan JR, Manuck SB, Adams MR, Williams JK, Register TC, Clarkson TB. Plaque changes and arterial enlargement in atherosclerotic monkeys after manipulation of diet and social environment. Arterioscler Thromb. 1993;13:254-263.
83. Joris I, Zand T, Nunnari JJ, Krolikowski FJ, Majno G. Studies on the pathogenesis of atherosclerosis, I: adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats. Am J Pathol. 1983;113:341-358.
84. Dillard A, Matthan NR, Lichtenstein AH. Use of hamster as a model to study diet-induced atherosclerosis. Nutr Metab (Lond). 2010;7:89. doi: 10.1186/1743-7075-7-89.
85. Mahley RW, Weisgraber KH. Canine lipoproteins and atherosclerosis, I: isolation and characterization of plasma lipoproteins from control dogs. Circ Res. 1974;35:713-721.
86. Mahley RW, Weisgraber KH, Innerarity T. Canine lipoproteins and atherosclerosis, II: characterization of the plasma lipoproteins associated with atherogenic and nonatherogenic hyperlipidemia. Circ Res. 1974;35:722-733.
87. St Clair RW. The contribution of avian models to our understanding of atherosclerosis and their promise for the future. Lab Anim Sci. 1998;48:565-568.
88. Stoletov K, Fang L, Choi SH, Hartvigsen K, Hansen LF, Hall C, Pattison J, Juliano J, Miller ER, Almazan F, Crosier P, Witztum JL, Klemke RL, Miller YI. Vascular lipid accumulation, lipoprotein oxidation, and macrophage lipid uptake in hypercholesterolemic zebrafish. Circ Res. 2009;104:952-960. doi: 10.1161/CIRCRESAHA.108.189803.
89. Lyngdorf LG, Gregersen S, Daugherty A, Falk E. Paradoxical reduction of atherosclerosis in apoE-deficient mice with obesity-related type 2 diabetes. Cardiovasc Res. 2003;59:854-862.
90. Al-Mashhadi RH, Bjørklund MM, Mortensen MB, Christoffersen C, Larsen T, Falk E, Bentzon JF. Diabetes with poor glycaemic control does not promote atherosclerosis in genetically modified hypercholesterolaemic minipigs. Diabetologia. 2015;58:1926-1936. doi: 10.1007/ s00125-015-3637-1.
91. Hsueh W, Abel ED, Breslow JL, Maeda N, Davis RC, Fisher EA, Dansky H, McClain DA, McIndoe R, Wassef MK, Rabadan-Diehl C, Goldberg IJ. Recipes for creating animal models of diabetic cardiovascular disease. Circ Res. 2007;100:1415-1427.
92. Galkina EV, Butcher M, Keller SR, Goff M, Bruce A, Pei H, Sarembock IJ, Sanders JM, Nagelin MH, Srinivasan S, Kulkarni RN, Hedrick CC, Lattanzio FA, Dobrian AD, Nadler JL, Ley K. Accelerated atherosclerosis in Apoe-/- mice heterozygous for the insulin receptor and the insulin receptor substrate-1. Arterioscler Thromb Vasc Biol. 2012;32:247-256. doi: 10.1161/ATVBAHA.111.240358.
93. Renard CB, Kramer F, Johansson F, Lamharzi N, Tannock LR, von Herrath MG, Chait A, Bornfeldt KE. Diabetes and diabetes-associated lipid abnormalities have distinct effects on initiation and progression of atherosclerotic lesions. J Clin Invest. 2004;114:659-668. doi: 10.1172/ JCI17867.
94. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32(suppl 3):S112-S119.
95. London GM, Drueke TB. Atherosclerosis and arteriosclerosis in chronic renal failure. Kidney Int. 1997;51:1678-1695.
96. Yang HC, Zuo Y, Fogo AB. Models of chronic kidney disease. Drug Discov Today Dis Models. 2010;7:13-19. doi: 10.1016/j. ddmod.2010.08.002.
97. Bro S, Bentzon JF, Falk E, Andersen CB, Olgaard K, Nielsen LB. Chronic renal failure accelerates atherogenesis in apolipoprotein E-deficient mice. J Am Soc Nephrol. 2003;14:2466-2474.
98. Chan DT, Irish AB, Dogra GK, Watts GF. Dyslipidaemia and cardiorenal disease: mechanisms, therapeutic opportunities and clinical trials. Atherosclerosis. 2008;196:823-834. doi: 10.1016/j. atherosclerosis.2007.01.023.
99. Suganuma E, Babaev VR, Motojima M, Zuo Y, Ayabe N, Fogo AB, Ichikawa I, Linton MF, Fazio S, Kon V. Angiotensin inhibition decreases progression of advanced atherosclerosis and stabilizes established atherosclerotic plaques. J Am Soc Nephrol. 2007;18:2311-2319. doi: 10.1681/ASN.2006090967.
100. Rosendorff C, Lackland DT, Allison M, Aronow WS, Black HR, Blumenthal RS, Cannon CP, de Lemos JA, Elliott WJ, Findeiss L, Gersh BJ, Gore JM, Levy D, Long JB, O'Connor CM, O'Gara PT, Ogedegbe G, Oparil S, White WB; on behalf of the American Heart Association, American College of Cardiology, and American Society of Hypertension. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension [published correction appears in Circulation. 2016;134:e260]. Circulation. 2015;131:e435-e470. doi: 10.1161/ CIR.0000000000000207.
101. Lackland DT, Roccella EJ, Deutsch AF, Fornage M, George MG, Howard G, Kissela BM, Kittner SJ, Lichtman JH, Lisabeth LD, Schwamm LH, Smith EE, Towfighi A; on behalf of the American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; Council on Functional Genomics and Translational Biology. Factors influencing the decline in stroke mortality: a statement from the American Heart Association/American Stroke Association. Stroke. 2014;45:315-353. doi: 10.1161/01.str.0000437068.30550.cf.
102. Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, Jones DW, Kurtz T, Sheps SG, Roccella EJ. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation. 2005;111:697-716. doi: 10.1161/01. CIR.0000154900.76284.F6.
103. Lu H, Cassis LA, Daugherty A. Atherosclerosis and arterial blood pressure in mice. Curr Drug Targets. 2007;8:1181-1189.
104. Kurtz TW, Griffin KA, Bidani AK, Davisson RL, Hall JE. Recommendations for blood pressure measurement in humans and experimental animals: part 2: blood pressure measurement in experimental animals: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Arterioscler Thromb Vasc Biol. 2005;25:e22-e33. doi: 10.1161/01. ATV.0000158419.98675.d7.
105. Daugherty A, Rateri D, Lu H, Balakrishnan A. Measuring blood pressure in mice using volume pressure recording, a tail-cuff method. J Vis Exp. 2009;27:e1291. doi: 10.3791/1291.
106. Chen J, Kuhlencordt PJ, Astern J, Gyurko R, Huang PL. Hypertension does not account for the accelerated atherosclerosis and development of aneurysms in male apolipoprotein E/endothelial nitric oxide synthase double knockout mice. Circulation. 2001;104:2391-2394.
107. Doran DE, Weiss D, Zhang Y, Griendling KK, Taylor WR. Differential effects of AT1 receptor and Ca2+ channel blockade on atherosclerosis, inflammatory gene expression, and production of reactive oxygen species. Atherosclerosis. 2007;195:39-47. doi: 10.1016/j.atherosclerosis. 2006.11.030.
108. Grundy SM. Obesity, metabolic syndrome, and coronary atherosclerosis. Circulation. 2002;105:2696-2698.
109. Keys A, Menotti A, Aravanis C, Blackburn H, Djordevic BS, Buzina R, Dontas AS, Fidanza F, Karvonen MJ, Kimura N. The Seven Countries Study: 2,289 deaths in 15 years. Prev Med. 1984;13:141-154.
110. Heller R, Garrison RJ, Havlik RJ, Feinleib M, Padgett S. Family resemblances in height and relative weight in the Framingham Heart Study. Int J Obes. 1984;8:399-405.
111. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837-1847.
112. Azimi A, Charlot MG, Torp-Pedersen C, Gislason GH, Køber L, Jensen LO, Thayssen P, Ravkilde J, Tilsted HH, Lassen JF, Thuesen L. Moderate overweight is beneficial and severe obesity detrimental for patients with documented atherosclerotic heart disease. Heart. 2013;99:655-660. doi: 10.1136/heartjnl-2012-303066.
113. Kennedy AJ, Ellacott KL, King VL, Hasty AH. Mouse models of the metabolic syndrome. Dis Model Mech. 2010;3:156-166. doi: 10.1242/ dmm.003467.
114. Hasty AH, Shimano H, Osuga J, Namatame I, Takahashi A, Yahagi N, Perrey S, Iizuka Y, Tamura Y, Amemiya-Kudo M, Yoshikawa T, Okazaki H, Ohashi K, Harada K, Matsuzaka T, Sone H, Gotoda T, Nagai R, Ishibashi S, Yamada N. Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor. J Biol Chem. 2001;276:37402-37408. doi: 10.1074/jbc.M010176200.
115. Gruen ML, Saraswathi V, Nuotio-Antar AM, Plummer MR, Coenen KR, Hasty AH. Plasma insulin levels predict atherosclerotic lesion burden in obese hyperlipidemic mice. Atherosclerosis. 2006;186:54-64. doi: 10.1016/j.atherosclerosis.2005.07.007.
116. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8:e1000412. doi: 10.1371/ journal.pbio.1000412.
117. Landis SC, Amara SG, Asadullah K, Austin CP, Blumenstein R, Bradley EW, Crystal RG, Darnell RB, Ferrante RJ, Fillit H, Finkelstein R, Fisher M, Gendelman HE, Golub RM, Goudreau JL, Gross RA, Gubitz AK, Hesterlee SE, Howells DW, Huguenard J, Kelner K, Koroshetz W, Krainc D, Lazic SE, Levine MS, Macleod MR, McCall JM, Moxley RT 3rd, Narasimhan K, Noble LJ, Perrin S, Porter JD, Steward O, Unger E, Utz U, Silberberg SD. A call for transparent reporting to optimize the predictive value of preclinical research. Nature. 2012;490:187-191. doi: 10.1038/nature11556.
118. National Institutes of Health. Principles and Guidelines for Reporting Preclinical Research. https://www.nih.gov/research-training/rigorreproducibility/ principles-guidelines-reporting-preclinical-research. Accessed February 5, 2016.
119. Paigen B, Mitchell D, Reue K, Morrow A, Lusis AJ, LeBoeuf RC. Ath-1, a gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice. Proc Natl Acad Sci U S A. 1987;84:3763-3767.
120. Spiezio SH, Amon LM, McMillen TS, Vick CM, Houston BA, Caldwell M, Ogimoto K, Morton GJ, Kirk EA, Schwartz MW, Nadeau JH, LeBoeuf RC. Genetic determinants of atherosclerosis, obesity, and energy balance in consomic mice. Mamm Genome. 2014;25:549-563. doi: 10.1007/s00335-014-9530-2.
121. Shi W, Wang NJ, Shih DM, Sun VZ, Wang X, Lusis AJ. Determinants of atherosclerosis susceptibility in the C3H and C57BL/6 mouse model: evidence for involvement of endothelial cells but not blood cells or cholesterol metabolism. Circ Res. 2000;86:1078-1084.
122. Teupser D, Persky AD, Breslow JL. Induction of atherosclerosis by low-fat, semisynthetic diets in LDL receptor-deficient C57BL/6J and FVB/NJ mice: comparison of lesions of the aortic root, brachiocephalic artery, and whole aorta (en face measurement). Arterioscler Thromb Vasc Biol. 2003;23:1907-1913. doi: 10.1161/01. ATV.0000090126.34881.B1.
123. Nicholson A, Reifsnyder PC, Malcolm RD, Lucas CA, MacGregor GR, Zhang W, Leiter EH. Diet-induced obesity in two C57BL/6 substrains with intact or mutant nicotinamide nucleotide transhydrogenase (Nnt) gene. Obesity (Silver Spring). 2010;18:1902-1905. doi: 10.1038/ oby.2009.477.
124. Lusis AJ, Yu J, Wang SS. The problem of passenger genes in transgenic mice. Arterioscler Thromb Vasc Biol. 2007;27:2100-2103. doi: 10.1161/ ATVBAHA.107.147918.
125. Paigen B, Holmes PA, Mitchell D, Albee D. Comparison of atherosclerotic lesions and HDL-lipid levels in male, female, and testosterone-treated female mice from strains C57BL/6, BALB/c, and C3H. Atherosclerosis. 1987;64:215-221.
126. Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M. Decreased atherosclerosis in mice deficient in both macrophage colonystimulating factor (op) and apolipoprotein E. Proc Natl Acad Sci U S A. 1995;92:8264-8268.
127. Tangirala RK, Rubin EM, Palinski W. Quantitation of atherosclerosis in murine models: correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein E-deficient mice. J Lipid Res. 1995;36:2320-2328.
128. Marsh MM, Walker VR, Curtiss LK, Banka CL. Protection against atherosclerosis by estrogen is independent of plasma cholesterol levels in LDL receptor-deficient mice. J Lipid Res. 1999;40:893-900.
129. Li AC, Brown KK, Silvestre MJ, Willson TM, Palinski W, Glass CK. Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J Clin Invest. 2000;106:523-531. doi: 10.1172/JCI10370.
130. King VL, Lin AY, Kristo F, Anderson TJ, Ahluwalia N, Hardy GJ, Owens AP 3rd, Howatt DA, Shen D, Tager AM, Luster AD, Daugherty A, Gerszten RE. Interferon-gamma and the interferon-inducible chemokine CXCL10 protect against aneurysm formation and rupture. Circulation. 2009;119:426-435. doi: 10.1161/CIRCULATIONAHA.108.785949.
131. Yi X, Xu L, Kim K, Kim HS, Maeda N. Genetic reduction of lipoic acid synthase expression modestly increases atherosclerosis in male, but not in female, apolipoprotein E-deficient mice. Atherosclerosis. 2010;211:424-430. doi: 10.1016/j.atherosclerosis.2010.03.009.
132. Whitman SC, Ravisankar P, Daugherty A. IFN-gamma deficiency exerts gender-specific effects on atherogenesis in apolipoprotein E-/- mice. J Interferon Cytokine Res. 2002;22:661-670. doi: 10.1089/10799900260100141.
133. Tsukamoto K, Tangirala R, Chun SH, Puré E, Rader DJ. Rapid regression of atherosclerosis induced by liver-directed gene transfer of ApoE in ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 1999;19:2162-2170.
134. Metzger D, Chambon P. Site-and time-specific gene targeting in the mouse. Methods. 2001;24:71-80. doi: 10.1006/meth.2001.1159.
135. Reis ED, Li J, Fayad ZA, Rong JX, Hansoty D, Aguinaldo JG, Fallon JT, Fisher EA. Dramatic remodeling of advanced atherosclerotic plaques of the apolipoprotein E-deficient mouse in a novel transplantation model. J Vasc Surg. 2001;34:541-547.
136. Chereshnev I, Trogan E, Omerhodzic S, Itskovich V, Aguinaldo JG, Fayad ZA, Fisher EA, Reis ED. Mouse model of heterotopic aortic arch transplantation. J Surg Res. 2003;111:171-176.
137. Trogan E, Feig JE, Dogan S, Rothblat GH, Angeli V, Tacke F, Randolph GJ, Fisher EA. Gene expression changes in foam cells and the role of chemokine receptor CCR7 during atherosclerosis regression in ApoEdeficient mice. Proc Natl Acad Sci U S A. 2006;103:3781-3786. doi: 10.1073/pnas.0511043103.
138. Llodrá J, Angeli V, Liu J, Trogan E, Fisher EA, Randolph GJ. Emigration of monocyte-derived cells from atherosclerotic lesions characterizes regressive, but not progressive, plaques. Proc Natl Acad Sci U S A. 2004;101:11779-11784. doi: 10.1073/pnas.0403259101.
139. Lieu HD, Withycombe SK, Walker Q, Rong JX, Walzem RL, Wong JS, Hamilton RL, Fisher EA, Young SG. Eliminating atherogenesis in mice by switching off hepatic lipoprotein secretion. Circulation. 2003;107:1315-1321.
140. Feig JE, Parathath S, Rong JX, Mick SL, Vengrenyuk Y, Grauer L, Young SG, Fisher EA. Reversal of hyperlipidemia with a genetic switch favorably affects the content and inflammatory state of macrophages in atherosclerotic plaques. Circulation. 2011;123:989-998. doi: 10.1161/ CIRCULATIONAHA.110.984146.
141. Potteaux S, Gautier EL, Hutchison SB, van Rooijen N, Rader DJ, Thomas MJ, Sorci-Thomas MG, Randolph GJ. Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe-/- mice during disease regression. J Clin Invest. 2011;121:2025-2036. doi: 10.1172/JCI43802.
142. Li R, Chao H, Ko KW, Cormier S, Dieker C, Nour EA, Wang S, Chan L, Oka K. Gene therapy targeting LDL cholesterol but not HDL cholesterol induces regression of advanced atherosclerosis in a mouse model of familial hypercholesterolemia. J Genet Syndr Gene Ther. 2011;2:106.
143. MacDougall ED, Kramer F, Polinsky P, Barnhart S, Askari B, Johansson F, Varon R, Rosenfeld ME, Oka K, Chan L, Schwartz SM, Bornfeldt KE. Aggressive very low-density lipoprotein (VLDL) and LDL lowering by gene transfer of the VLDL receptor combined with a low-fat diet regimen induces regression and reduces macrophage content in advanced atherosclerotic lesions in LDL receptor-deficient mice. Am J Pathol. 2006;168:2064-2073.
144. Oka K, Belalcazar LM, Dieker C, Nour EA, Nuno-Gonzalez P, Paul A, Cormier S, Shin JK, Finegold M, Chan L. Sustained phenotypic correction in a mouse model of hypoalphalipoproteinemia with a helperdependent adenovirus vector [published correction appears in Gene Ther. 2007;14:845]. Gene Ther. 2007;14:191-202. doi: 10.1038/ sj.gt.3302819.
145. Horton JD, Cohen JC, Hobbs HH. PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res. 2009;50(suppl):S172-S177. doi: 10.1194/ jlr.R800091-JLR200.
146. Fan D, Yancey PG, Qiu S, Ding L, Weeber EJ, Linton MF, Fazio S. Self-association of human PCSK9 correlates with its LDLR-degrading activity. Biochemistry. 2008;47:1631-1639. doi: 10.1021/bi7016359.
147. Zhang DW, Garuti R, Tang WJ, Cohen JC, Hobbs HH. Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc Natl Acad Sci U S A. 2008;105:13045-13050. doi: 10.1073/pnas.0806312105.
148. Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derré A, Villéger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154-156. doi: 10.1038/ng1161.
149. Rios J, Stein E, Shendure J, Hobbs HH, Cohen JC. Identification by whole-genome resequencing of gene defect responsible for severe hypercholesterolemia. Hum Mol Genet. 2010;19:4313-4318. doi: 10.1093/hmg/ddq352.
150. Bjørklund MM, Hollensen AK, Hagensen MK, Dagnaes-Hansen F, Christoffersen C, Mikkelsen JG, Bentzon JF. Induction of atherosclerosis in mice and hamsters without germline genetic engineering. Circ Res. 2014;114:1684-1689. doi: 10.1161/CIRCRESAHA.114.302937.
151. Roche-Molina M, Sanz-Rosa D, Cruz FM, García-Prieto J, López S, Abia R, Muriana FJ, Fuster V, Ibáñez B, Bernal JA. Induction of sustained hypercholesterolemia by single adeno-associated virus-mediated gene transfer of mutant hPCSK9. Arterioscler Thromb Vasc Biol. 2015;35:50-59. doi: 10.1161/ATVBAHA.114.303617.
152. Lu H, Howatt DA, Balakrishnan A, Graham MJ, Mullick AE, Daugherty A. Hypercholesterolemia induced by a PCSK9 gain-of-function mutation augments angiotensin II-induced abdominal aortic aneurysms in C57BL/6 mice: brief report. Arterioscler Thromb Vasc Biol. 2016;36:1753-1757. doi: 10.1161/ATVBAHA.116.307613.
153. Goettsch C, Hutcheson JD, Hagita S, Rogers MA, Creager MD, Pham T, Choi J, Mlynarchik AK, Pieper B, Kjolby M, Aikawa M, Aikawa E. A single injection of gain-of-function mutant PCSK9 adeno-associated virus vector induces cardiovascular calcification in mice with no genetic modification. Atherosclerosis. 2016;251:109-118. doi: 10.1016/j. atherosclerosis.2016.06.011.
154. Goettsch C, Hutcheson JD, Aikawa M, Iwata H, Pham T, Nykjaer A, Kjolby M, Rogers M, Michel T, Shibasaki M, Hagita S, Kramann R, Rader DJ, Libby P, Singh SA, Aikawa E. Sortilin mediates vascular calcification via its recruitment into extracellular vesicles. J Clin Invest. 2016;126:1323-1336. doi: 10.1172/JCI80851.
155. Rashid S, Tavori H, Brown PE, Linton MF, He J, Giunzioni I, Fazio S. Proprotein convertase subtilisin kexin type 9 promotes intestinal overproduction of triglyceride-rich apolipoprotein B lipoproteins through both low-density lipoprotein receptor-dependent and-independent mechanisms [published correction appears in Circulation. 2015;131:e429]. Circulation. 2014;130:431-441. doi: 10.1161/ CIRCULATIONAHA.113.006720.
156. Daugherty A, Tabas I, Rader DJ. Accelerating the pace of atherosclerosis research. Arterioscler Thromb Vasc Biol. 2015;35:11-12. doi: 10.1161/ATVBAHA.114.304833.
157. Lu H, Daugherty A. Atherosclerosis: cell biology and lipoproteins. Curr Opin Lipidol. 2015;26:152-153. doi: 10.1097/MOL. 0000000000000166.
158. Hewing B, Parathath S, Mai CK, Fiel MI, Guo L, Fisher EA. Rapid regression of atherosclerosis with MTP inhibitor treatment. Atherosclerosis. 2013;227:125-129. doi: 10.1016/j.atherosclerosis.2012.12.026.
159. Bartels ED, Christoffersen C, Lindholm MW, Nielsen LB. Altered metabolism of LDL in the arterial wall precedes atherosclerosis regression. Circ Res. 2015;117:933-942.
160. Harats D, Shaish A, George J, Mulkins M, Kurihara H, Levkovitz H, Sigal E. Overexpression of 15-lipoxygenase in vascular endothelium accelerates early atherosclerosis in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2000;20:2100-2105.
161. Song L, Leung C, Schindler C. Lymphocytes are important in early atherosclerosis. J Clin Invest. 2001;108:251-259. doi: 10.1172/JCI11380.
162. Tabas I. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency. Arterioscler Thromb Vasc Biol. 2005;25:2255-2264. doi: 10.1161/01.ATV.0000184783.04864.9f.
163. Rudel LL, Parks JS, Hedrick CC, Thomas M, Williford K. Lipoprotein and cholesterol metabolism in diet-induced coronary artery atherosclerosis in primates: role of cholesterol and fatty acids. Prog Lipid Res. 1998;37:353-370.
164. Fan J, Kitajima S, Watanabe T, Xu J, Zhang J, Liu E, Chen YE. Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine. Pharmacol Ther. 2015;146:104-119. doi: 10.1016/j.pharmthera.2014.09.009.
165. Paigen B, Morrow A, Brandon C, Mitchell D, Holmes P. Variation in susceptibility to atherosclerosis among inbred strains of mice. Atherosclerosis. 1985;57:65-73.
166. Lichtman AH, Clinton SK, Iiyama K, Connelly PW, Libby P, Cybulsky MI. Hyperlipidemia and atherosclerotic lesion development in LDL receptor-deficient mice fed defined semipurified diets with and without cholate. Arterioscler Thromb Vasc Biol. 1999;19:1938-1944.
167. Hartvigsen K, Binder CJ, Hansen LF, Rafia A, Juliano J, Hörkkö S, Steinberg D, Palinski W, Witztum JL, Li AC. A diet-induced hypercholesterolemic murine model to study atherogenesis without obesity and metabolic syndrome. Arterioscler Thromb Vasc Biol. 2007;27:878-885. doi: 10.1161/01.ATV.0000258790.35810.02.
168. Kritchevsky D. Dietary fat and experimental atherosclerosis. Int J Tissue React. 1991;13:59-65.
169. Sparks JD, Sparks CE, Kritchevsky D. Hypercholesterolemia and aortic glycosaminoglycans of rabbits fed semi-purified diets containing sucrose and lactose. Atherosclerosis. 1986;60:183-196.
170. Srivastava U, Paigen BJ, Korstanje R. Differences in health status affect susceptibility and mapping of genetic loci for atherosclerosis (fatty streak) in inbred mice. Arterioscler Thromb Vasc Biol. 2012;32:2380-2386. doi: 10.1161/ATVBAHA.112.255703.
171. Giles DA, Ramkhelawon B, Donelan EM, Stankiewicz TE, Hutchison SB, Mukherjee R, Cappelletti M, Karns R, Karp CL, Moore KJ, Divanovic S. Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice. Mol Metab. 2016;5:1121-1130. doi: 10.1016/j.molmet.2016.09.008.
172. Tian XY, Ganeshan K, Hong C, Nguyen KD, Qiu Y, Kim J, Tangirala RK, Tontonoz P, Tonotonoz P, Chawla A. Thermoneutral housing accelerates metabolic inflammation to potentiate atherosclerosis but not insulin resistance [published correction appears in Cell Metab. 2016;23:386]. Cell Metab. 2016;23:165-178. doi: 10.1016/j. cmet.2015.10.003.
173. Tang WH, Hazen SL. The contributory role of gut microbiota in cardiovascular disease. J Clin Invest. 2014;124:4204-4211. doi: 10.1172/JCI72331.
174. Gregory JC, Buffa JA, Org E, Wang Z, Levison BS, Zhu W, Wagner MA, Bennett BJ, Li L, DiDonato JA, Lusis AJ, Hazen SL. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290:5647-5660. doi: 10.1074/jbc.M114.618249.
175. Stappenbeck TS, Virgin HW. Accounting for reciprocal host-microbiome interactions in experimental science. Nature. 2016;534:191-199. doi: 10.1038/nature18285.
176. Boisvert WA, Spangenberg J, Curtiss LK. Role of leukocyte-specific LDL receptors on plasma lipoprotein cholesterol and atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 1997;17:340-347.
177. Herijgers N, Van Eck M, Groot PH, Hoogerbrugge PM, Van Berkel TJ. Low density lipoprotein receptor of macrophages facilitates atherosclerotic lesion formation in C57Bl/6 mice. Arterioscler Thromb Vasc Biol. 2000;20:1961-1967.
178. Linton MF, Babaev VR, Gleaves LA, Fazio S. A direct role for the macrophage low density lipoprotein receptor in atherosclerotic lesion formation. J Biol Chem. 1999;274:19204-19210.
179. Schiller NK, Kubo N, Boisvert WA, Curtiss LK. Effect of gamma-irradiation and bone marrow transplantation on atherosclerosis in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2001;21:1674-1680.
180. Sata M, Saiura A, Kunisato A, Tojo A, Okada S, Tokuhisa T, Hirai H, Makuuchi M, Hirata Y, Nagai R. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med. 2002;8:403-409. doi: 10.1038/nm0402-403.
181. Hu Y, Zhang Z, Torsney E, Afzal AR, Davison F, Metzler B, Xu Q. Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice. J Clin Invest. 2004;113:1258-1265. doi: 10.1172/JCI19628.
182. Bentzon JF, Weile C, Sondergaard CS, Hindkjaer J, Kassem M, Falk E. Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in ApoE knockout mice. Arterioscler Thromb Vasc Biol. 2006;26:2696-2702. doi: 10.1161/01. ATV.0000247243.48542.9d.
183. Hagensen MK, Shim J, Thim T, Falk E, Bentzon JF. Circulating endothelial progenitor cells do not contribute to plaque endothelium in murine atherosclerosis. Circulation. 2010;121:898-905. doi: 10.1161/ CIRCULATIONAHA.109.885459.
184. Rader DJ, Daugherty A. Translating molecular discoveries into new therapies for atherosclerosis. Nature. 2008;451:904-913. doi: 10.1038/ nature06796.
185. Scanu AM, Wisdom C. Serum lipoproteins structure and function. Annu Rev Biochem. 1972;41:703-730. doi: 10.1146/annurev. bi.41.070172.003415.
186. Wang S, Subramanian V, Lu H, Howatt DA, Moorleghen JJ, Charnigo R, Cassis LA, Daugherty A. Deficiency of receptor-associated protein attenuates angiotensin II-induced atherosclerosis in hypercholesterolemic mice without influencing abdominal aortic aneurysms [published correction appears in Atherosclerosis. 2013;230:300]. Atherosclerosis. 2012;220:375-380. doi: 10.1016/j.atherosclerosis.2011.11.013.
187. Daugherty A, Cornicelli JA, Welch K, Sendobry SM, Rateri DL. Scavenger receptors are present on rabbit aortic endothelial cells in vivo. Arterioscler Thromb Vasc Biol. 1997;17:2369-2375.
188. Paigen B, Morrow A, Holmes PA, Mitchell D, Williams RA. Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis. 1987;68:231-240.
189. Daugherty A, Whitman SC. Quantification of atherosclerosis in mice. Methods Mol Biol. 2003;209:293-309.
190. Baglione J, Smith JD. Quantitative assay for mouse atherosclerosis in the aortic root. Methods Mol Med. 2006;129:83-95. doi: 10.1385/1-59745-213-0:83.
191. Choy K, Beck K, Png FY, Wu BJ, Leichtweis SB, Thomas SR, Hou JY, Croft KD, Mori TA, Stocker R. Processes involved in the site-specific effect of probucol on atherosclerosis in apolipoprotein E gene knockout mice. Arterioscler Thromb Vasc Biol. 2005;25:1684-1690. doi: 10.1161/01.ATV.0000174125.89058.b6.
192. Goel R, Schrank BR, Arora S, Boylan B, Fleming B, Miura H, Newman PJ, Molthen RC, Newman DK. Site-specific effects of PECAM-1 on atherosclerosis in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2008;28:1996-2002. doi: 10.1161/ATVBAHA.108.172270.
193. Witting PK, Pettersson K, Letters J, Stocker R. Site-specific antiatherogenic effect of probucol in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2000;20:E26-E33.
194. Barry-Lane PA, Patterson C, van der Merwe M, Hu Z, Holland SM, Yeh ET, Runge MS. p47phox is required for atherosclerotic lesion progression in ApoE-/- mice. J Clin Invest. 2001;108:1513-1522. doi: 10.1172/ JCI11927.
195. Hu W, Polinsky P, Sadoun E, Rosenfeld ME, Schwartz SM. Atherosclerotic lesions in the common coronary arteries of ApoE knockout mice. Cardiovasc Pathol. 2005;14:120-125. doi: 10.1016/j. carpath.2005.02.004.
196. Daugherty A, Rateri DL. Development of experimental designs for atherosclerosis studies in mice. Methods. 2005;36:129-138. doi: 10.1016/j. ymeth.2004.11.008.
197. Rosenfeld ME, Polinsky P, Virmani R, Kauser K, Rubanyi G, Schwartz SM. Advanced atherosclerotic lesions in the innominate artery of the ApoE knockout mouse. Arterioscler Thromb Vasc Biol. 2000;20:2587-2592.
198. Di Gregoli K, Jenkins N, Salter R, White S, Newby AC, Johnson JL. MicroRNA-24 regulates macrophage behavior and retards atherosclerosis. Arterioscler Thromb Vasc Biol. 2014;34:1990-2000. doi: 10.1161/ ATVBAHA.114.304088.
199. Reardon CA, Blachowicz L, Lukens J, Nissenbaum M, Getz GS. Genetic background selectively influences innominate artery atherosclerosis: immune system deficiency as a probe. Arterioscler Thromb Vasc Biol. 2003;23:1449-1454. doi: 10.1161/01.ATV.0000079793.58054.2E.
200. Sontag TJ, Krishack PA, Lukens JR, Bhanvadia CV, Getz GS, Reardon CA. Apolipoprotein A-I protection against atherosclerosis is dependent on genetic background. Arterioscler Thromb Vasc Biol. 2014;34:262-269. doi: 10.1161/ATVBAHA.113.302831.
201. Daugherty A, Zweifel BS, Schonfeld G. The effects of probucol on the progression of atherosclerosis in mature Watanabe heritable hyperlipidaemic rabbits. Br J Pharmacol. 1991;103:1013-1018.
202. Khanicheh E, Qi Y, Xie A, Mitterhuber M, Xu L, Mochizuki M, Daali Y, Jaquet V, Krause KH, Ruggeri ZM, Kuster GM, Lindner JR, Kaufmann BA. Molecular imaging reveals rapid reduction of endothelial activation in early atherosclerosis with apocynin independent of antioxidative properties. Arterioscler Thromb Vasc Biol. 2013;33:2187-2192. doi: 10.1161/ATVBAHA.113.301710.
203. Segers FM, den Adel B, Bot I, van der Graaf LM, van der Veer EP, Gonzalez W, Raynal I, de Winther M, Wodzig WK, Poelmann RE, van Berkel TJ, van der Weerd L, Biessen EA. Scavenger receptor-AI-targeted iron oxide nanoparticles for in vivo MRI detection of atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2013;33:1812-1819. doi: 10.1161/ATVBAHA.112.300707.
204. Li X, Bauer W, Israel I, Kreissl MC, Weirather J, Richter D, Bauer E, Herold V, Jakob P, Buck A, Frantz S, Samnick S. Targeting P-selectin by gallium-68-labeled fucoidan positron emission tomography for noninvasive characterization of vulnerable plaques: correlation with in vivo 17.6T MRI. Arterioscler Thromb Vasc Biol. 2014;34:1661-1667. doi: 10.1161/ATVBAHA.114.303485.
205. Keliher EJ, Ye YX, Wojtkiewicz GR, Aguirre AD, Tricot B, Senders ML, Groenen H, Fay F, Perez-Medina C, Calcagno C, Carlucci G, Reiner T, Sun Y, Courties G, Iwamoto Y, Kim HY, Wang C, Chen JW, Swirski FK, Wey HY, Hooker J, Fayad ZA, Mulder WJ, Weissleder R, Nahrendorf M. Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease. Nat Commun. 2017;8:14064. doi: 10.1038/ncomms14064.
206. Nahrendorf M, Zhang H, Hembrador S, Panizzi P, Sosnovik DE, Aikawa E, Libby P, Swirski FK, Weissleder R. Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis. Circulation. 2008;117:379-387. doi: 10.1161/CIRCULATIONAHA.107.741181.
207. Cuadrado I, Saura M, Castejón B, Martin AM, Herruzo I, Balatsos N, Zamorano JL, Zaragoza C. Preclinical models of atherosclerosis: the future of hybrid PET/MR technology for the early detection of vulnerable plaque. Expert Rev Mol Med. 2016;18:e6. doi: 10.1017/erm.2016.5.
208. Lin JB, Phillips EH, Riggins TE, Sangha GS, Chakraborty S, Lee JY, Lycke RJ, Hernandez CL, Soepriatna AH, Thorne BR, Yrineo AA, Goergen CJ. Imaging of small animal peripheral artery disease models: recent advancements and translational potential. Int J Mol Sci. 2015;16:11131-11177. doi: 10.3390/ijms160511131.
209. Ylä-Herttuala S, Bentzon JF, Daemen M, Falk E, Garcia-Garcia HM, Herrmann J, Hoefer I, Jukema JW, Krams R, Kwak BR, Marx N, Naruszewicz M, Newby A, Pasterkamp G, Serruys PW, Waltenberger J, Weber C, Tokgözoglu L. Stabilisation of atherosclerotic plaques: position paper of the European Society of Cardiology (ESC) Working Group on atherosclerosis and vascular biology. Thromb Haemost. 2011;106:1-19. doi: 10.1160/TH10-12-0784.
210. Frank JS, Fogelman AM. Ultrastructure of the intima in WHHL and cholesterol-fed rabbit aortas prepared by ultra-rapid freezing and freezeetching. J Lipid Res. 1989;30:967-978.
211. Jerome WG. Lysosomes, cholesterol and atherosclerosis. Clin Lipidol. 2010;5:853-865. doi: 10.2217/clp.10.70.
212. Wolfe MS, Sawyer JK, Morgan TM, Bullock BC, Rudel LL. Dietary polyunsaturated fat decreases coronary artery atherosclerosis in a pediatric-aged population of African green monkeys. Arterioscler Thromb. 1994;14:587-597.
213. Tangirala RK, Mahlberg FH, Glick JM, Jerome WG, Rothblat GH. Lysosomal accumulation of unesterified cholesterol in model macrophage foam cells. J Biol Chem. 1993;268:9653-9660.
214. Rong JX, Blachford C, Feig JE, Bander I, Mayne J, Kusunoki J, Miller C, Davis M, Wilson M, Dehn S, Thorp E, Tabas I, Taubman MB, Rudel LL, Fisher EA. ACAT inhibition reduces the progression of preexisting, advanced atherosclerotic mouse lesions without plaque or systemic toxicity. Arterioscler Thromb Vasc Biol. 2013;33:4-12. doi: 10.1161/ ATVBAHA.112.252056.
215. Fazio S, Major AS, Swift LL, Gleaves LA, Accad M, Linton MF, Farese RV Jr. Increased atherosclerosis in LDL receptor-null mice lacking ACAT1 in macrophages. J Clin Invest. 2001;107:163-171. doi: 10.1172/ JCI10310.
216. Lu H, Rateri DL, Daugherty A. Immunostaining of mouse atherosclerotic lesions. Methods Mol Med. 2007;139:77-94.
217. Buchwalow I, Samoilova V, Boecker W, Tiemann M. Non-specific binding of antibodies in immunohistochemistry: fallacies and facts. Sci Rep. 2011;1:28. doi: 10.1038/srep00028.
218. Michel MC, Wieland T, Tsujimoto G. How reliable are G-proteincoupled receptor antibodies? Naunyn Schmiedebergs Arch Pharmacol. 2009;379:385-388. doi: 10.1007/s00210-009-0395-y.
219. Benicky J, Hafko R, Sanchez-Lemus E, Aguilera G, Saavedra JM. Six commercially available angiotensin II AT1 receptor antibodies are non-specific. Cell Mol Neurobiol. 2012;32:1353-1365. doi: 10.1007/ s10571-012-9862-y.
220. Shankman LS, Gomez D, Cherepanova OA, Salmon M, Alencar GF, Haskins RM, Swiatlowska P, Newman AA, Greene ES, Straub AC, Isakson B, Randolph GJ, Owens GK. KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis [published correction appears in Nat Med. 2016;22:217]. Nat Med. 2015;21:628-637. doi: 10.1038/nm.3866.
221. Campbell JH, Campbell GR. The cell biology of atherosclerosis: new developments. Aust N Z J Med. 1997;27:497-500.
222. Majesky MW, Dong XR, Hoglund V, Mahoney WM Jr, Daum G. The adventitia: a dynamic interface containing resident progenitor cells. Arterioscler Thromb Vasc Biol. 2011;31:1530-1539. doi: 10.1161/ ATVBAHA.110.221549.
223. Rattazzi M, Bennett BJ, Bea F, Kirk EA, Ricks JL, Speer M, Schwartz SM, Giachelli CM, Rosenfeld ME. Calcification of advanced atherosclerotic lesions in the innominate arteries of ApoE-deficient mice: potential role of chondrocyte-like cells. Arterioscler Thromb Vasc Biol. 2005;25:1420-1425. doi: 10.1161/01.ATV.0000166600.58468.1b.
224. Vengrenyuk Y, Nishi H, Long X, Ouimet M, Savji N, Martinez FO, Cassella CP, Moore KJ, Ramsey SA, Miano JM, Fisher EA. Cholesterol loading reprograms the microRNA-143/145-myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype. Arterioscler Thromb Vasc Biol. 2015;35:535-546. doi: 10.1161/ ATVBAHA.114.304029.
225. Wu C, Daugherty A, Lu H. A color segmentation based method to quantify atherosclerotic lesion compositions with immunostaining. Methods Mol Biol. 2017; 1614:21-30
226. Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R. Concept of vulnerable/ unstable plaque. Arterioscler Thromb Vasc Biol. 2010;30:1282-1292. doi: 10.1161/ATVBAHA.108.179739.
227. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995;92:657-671.
228. Thim T, Hagensen MK, Bentzon JF, Falk E. From vulnerable plaque to atherothrombosis. J Intern Med. 2008;263:506-516. doi: 10.1111/j.1365-2796.2008.01947.x.
229. Kolodgie FD, Burke AP, Farb A, Gold HK, Yuan J, Narula J, Finn AV, Virmani R. The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr Opin Cardiol. 2001;16:285-292.
230. Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R. Update on acute coronary syndromes: the pathologists' view. Eur Heart J. 2013;34:719-728. doi: 10.1093/eurheartj/ehs411.
231. Falk E, Schwartz SM, Galis ZS, Rosenfeld ME. Putative murine models of plaque rupture. Arterioscler Thromb Vasc Biol. 2007;27:969-972. doi: 10.1161/01.ATV.0000261572.33474.e0.
232. Jackson CL, Bennett MR, Biessen EA, Johnson JL, Krams R. Assessment of unstable atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2007;27:714-720. doi: 10.1161/01.ATV.0000261873.86623. e1.
233. Schwartz SM, Galis ZS, Rosenfeld ME, Falk E. Plaque rupture in humans and mice. Arterioscler Thromb Vasc Biol. 2007;27:705-713. doi: 10.1161/01.ATV.0000261709.34878.20.
234. Galkina E, Kadl A, Sanders J, Varughese D, Sarembock IJ, Ley K. Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent. J Exp Med. 2006;203:1273-1282. doi: 10.1084/jem.20052205.
235. Rosenfeld ME, Khoo JC, Miller E, Parthasarathy S, Palinski W, Witztum JL. Macrophage-derived foam cells freshly isolated from rabbit atherosclerotic lesions degrade modified lipoproteins, promote oxidation of low-density lipoproteins, and contain oxidation-specific lipid-protein adducts. J Clin Invest. 1991;87:90-99. doi: 10.1172/JCI115006.
236. Trogan E, Choudhury RP, Dansky HM, Rong JX, Breslow JL, Fisher EA. Laser capture microdissection analysis of gene expression in macrophages from atherosclerotic lesions of apolipoprotein E-deficient mice. Proc Natl Acad Sci U S A. 2002;99:2234-2239. doi: 10.1073/pnas.042683999.
237. Trogan E, Fisher EA. Laser capture microdissection for analysis of macrophage gene expression from atherosclerotic lesions. Methods Mol Biol. 2005;293:221-231.
238. Beer M, Doepping S, Hildner M, Weber G, Grabner R, Hu D, Mohanta SK, Srikakulapu P, Weih F, Habenicht AJ. Laser-capture microdissection of hyperlipidemic/ApoE-/- mouse aorta atherosclerosis. Methods Mol Biol. 2011;755:417-428. doi: 10.1007/978-1-61779-163-5-35.
239. Feig JE, Fisher EA. Laser capture microdissection for analysis of macrophage gene expression from atherosclerotic lesions. Methods Mol Biol. 2013;1027:123-135. doi: 10.1007/978-1-60327-369-5-5.
240. Volger OL, Fledderus JO, Kisters N, Fontijn RD, Moerland PD, Kuiper J, van Berkel TJ, Bijnens AP, Daemen MJ, Pannekoek H, Horrevoets AJ. Distinctive expression of chemokines and transforming growth factorbeta signaling in human arterial endothelium during atherosclerosis. Am J Pathol. 2007;171:326-337.
241. Won D, Zhu SN, Chen M, Teichert AM, Fish JE, Matouk CC, Bonert M, Ojha M, Marsden PA, Cybulsky MI. Relative reduction of endothelial nitric-oxide synthase expression and transcription in atherosclerosis-prone regions of the mouse aorta and in an in vitro model of disturbed flow. Am J Pathol. 2007;171:1691-1704. doi: 10.2353/ ajpath.2007.060860.
242. Ramsey SA, Vengrenyuk Y, Menon P, Podolsky I, Feig JE, Aderem A, Fisher EA, Gold ES. Epigenome-guided analysis of the transcriptome of plaque macrophages during atherosclerosis regression reveals activation of the Wnt signaling pathway. PLoS Genet. 2014;10:e1004828. doi: 10.1371/journal.pgen.1004828.
243. Wolber PK, Collins PJ, Lucas AB, De Witte A, Shannon KW. The Agilent in situ-synthesized microarray platform. Methods Enzymol. 2006;410:28-57. doi: 10.1016/S0076-6879(06)10002-6.
244. Fan JB, Gunderson KL, Bibikova M, Yeakley JM, Chen J, Wickham Garcia E, Lebruska LL, Laurent M, Shen R, Barker D. Illumina universal bead arrays. Methods Enzymol. 2006;410:57-73. doi: 10.1016/ S0076-6879(06)10003-8.
245. Dalma-Weiszhausz DD, Warrington J, Tanimoto EY, Miyada CG. The Affymetrix GeneChip platform: an overview. Methods Enzymol. 2006;410:3-28. doi: 10.1016/S0076-6879(06)10001-4.
246. Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009;10:57-63. doi: 10.1038/nrg2484.
247. Qin S, Kim J, Arafat D, Gibson G. Effect of normalization on statistical and biological interpretation of gene expression profiles. Front Genet. 2012;3:160. doi: 10.3389/fgene.2012.00160.
248. Wallenstein S, Zucker CL, Fleiss JL. Some statistical methods useful in circulation research. Circ Res. 1980;47:1-9.
249. Glantz SA. Biostatistics: how to detect, correct and prevent errors in the medical literature. Circulation. 1980;61:1-7.