Recent insights into the cellular biology of atherosclerosis

Journal of Cell Biology

Volumn 209, Issue 1, 2015, Pages 13-22

  Tabas, Ira ^a   García Cardeña, Guillermo ^b,c   Owens, Gary K ^d  

^a NewYork Presbyterian Hospital   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d UNIVERSITY OF VIRGINIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA METHYLTRANSFERASE 1; KRUPPEL LIKE FACTOR 2; KRUPPEL LIKE FACTOR 4; SYNDECAN 4;

APOPTOSIS; ATHEROGENESIS; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; CALCIUM TRANSPORT; CARDIOVASCULAR RISK; CELL DIFFERENTIATION; CELL FATE; CELL FUNCTION; CELL MEMBRANE; CELL MIGRATION; CELL PROLIFERATION; CYTOLOGY; DNA METHYLATION; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM CELL; EXOCYTOSIS; EXTRACELLULAR MATRIX; GLYCOCALYX; HUMAN; ION CURRENT; MACROPHAGE; MECHANOTRANSDUCTION; NONHUMAN; OXIDATIVE STRESS; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; SHEAR STRESS; SMOOTH MUSCLE FIBER; UNFOLDED PROTEIN RESPONSE; VASCULAR ENDOTHELIUM; ANIMAL; IMMUNOLOGY; PATHOLOGY; PHYSIOLOGY; SMOOTH MUSCLE CELL; VASCULAR SMOOTH MUSCLE;

ANIMALS; ATHEROSCLEROSIS; ENDOTHELIAL CELLS; ENDOTHELIUM, VASCULAR; HUMANS; MACROPHAGES; MECHANOTRANSDUCTION, CELLULAR; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE;

EID: 84928254049     PISSN: 00219525     EISSN: 15408140     Source Type: Journal    
DOI: 10.1083/jcb.201412052     Document Type: Review

References (107)

1. Abe, J., and B.C. Berk. 2014. Novel mechanisms of endothelial mechanotransduction. Arterioscler. Thromb. Vasc. Biol. 34:2378-2386. http://dx.doi.org/10.1161/ATVBAHA.114.303428
2. Alexander, M.R., and G.K. Owens. 2012. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Annu. Rev. Physiol. 74:13-40. http://dx.doi.org/10.1146/annurev-physiol-012110-142315
3. Alexander, M.R., C.W. Moehle, J.L. Johnson, Z. Yang, J.K. Lee, C.L. Jackson, and G.K. Owens. 2012. Genetic inactivation of IL-1 signaling enhances atherosclerotic plaque instability and reduces outward vessel remodeling in advanced atherosclerosis in mice. J. Clin. Invest. 122:70-79. http://dx.doi.org/10.1172/JCI43713
4. Allahverdian, S., A.C. Chehroudi, B.M. McManus, T. Abraham, and G.A. Francis. 2014. Contribution of intimal smooth muscle cells to cholesterol accumulation and macrophage-like cells in human atherosclerosis. Circulation. 129:1551-1559. http://dx.doi.org/10.1161/CIRCULATIONAHA.113.005015
5. Atkins, G.B., and D.I. Simon. 2013. Interplay between NF-κB and Kruppellike factors in vascular inflammation and atherosclerosis: location, location, location. J Am Heart Assoc. 2:e000290. http://dx.doi.org/10.1161/JAHA113.000290
6. Atkins, G.B., Y. Wang, G.H. Mahabeleshwar, H. Shi, H. Gao, D. Kawanami, V. Natesan, Z. Lin, D.I. Simon, and M.K. Jain. 2008. Hemizygous deficiency of Krüppel-like factor 2 augments experimental atherosclerosis. Circ. Res. 103:690-693. http://dx.doi.org/10.1161/CIRCRESAHA.108.184663
7. Baeyens, N., M.J. Mulligan-Kehoe, F. Corti, D.D. Simon, T.D. Ross, J.M. Rhodes, T.Z. Wang, C.O. Mejean, M. Simons, J. Humphrey, and M.A. Schwartz 2014. Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling. Proc. Natl. Acad. Sci. USA. 111:17308-17313. http://dx.doi.org/10.1073/pnas.1413725111
8. Bentzon, J.F., C. Weile, C.S. Sondergaard, J. Hindkjaer, M. Kassem, and E. Falk 2006. Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in ApoE knockout mice. Arterioscler. Thromb. Vasc. Biol. 26:2696-2702. http://dx.doi.org/10.1161/01.ATV.0000247243.48542.9d
9. Bornfeldt, K.E., and I. Tabas. 2011. Insulin resistance, hyperglycemia, and atherosclerosis. Cell Metab. 14:575-585. http://dx.doi.org/10.1016/j.cmet.2011.07.015
10. Braunwald, E. 1997. Shattuck lecture-cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N. Engl. J. Med. 337:1360-1369. http://dx.doi.org/10.1056/NEJM199711063371906
11. Bu, D.X., M. Tarrio, N. Grabie, Y. Zhang, H. Yamazaki, G. Stavrakis, E. Maganto-Garcia, Z. Pepper-Cunningham, P. Jarolim, M. Aikawa, et al. 2010. Statin-induced Krüppel-like factor 2 expression in human and mouse T cells reduces inflammatory and pathogenic responses. J. Clin. Invest 120:1961-1970. http://dx.doi.org/10.1172/JCI41384
12. Buckley, C.D., D.W. Gilroy, and C.N. Serhan. 2014. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity. 40:315-327. http://dx.doi.org/10.1016/j.immuni.2014.02.009
13. Caplice, N.M., T.J. Bunch, P.G. Stalboerger, S. Wang, D. Simper, D.V. Miller, S.J. Russell, M.R. Litzow, and W.D. Edwards. 2003. Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation. Proc. Natl. Acad. Sci. USA. 100:4754-4759. http://dx.doi.org/10.1073/pnas.0730743100
14. Civelek, M., E. Manduchi, R.J. Riley, C.J. Stoeckert Jr., and P.F. Davies. 2009. Chronic endoplasmic reticulum stress activates unfolded protein response in arterial endothelium in regions of susceptibility to atherosclerosis. Circ. Res. 105:453-461. http://dx.doi.org/10.1161/CIRCRESAHA109.203711
15. Conway, D.E., and M.A. Schwartz. 2013. Flow-dependent cellular mechanotransduction in atherosclerosis. J. Cell Sci. 126:5101-5109. http://dx.doi.org/10.1242/jcs.138313
16. Dai, G., M.R. Kaazempur-Mofrad, S. Natarajan, Y. Zhang, S. Vaughn, B.R. Blackman, R.D. Kamm, G. García-Cardeña, and M.A. Gimbrone Jr. 2004. Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc. Natl. Acad. Sci. USA. 101:14871-14876. http://dx.doi.org/10.1073/pnas.0406073101
17. Das, H., A. Kumar, Z. Lin, W.D. Patino, P.M. Hwang, M.W. Feinberg, P.K. Majumder, and M.K. Jain. 2006. Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes. Proc. Natl. Acad. Sci. USA. 103:6653-6658. http://dx.doi.org/10.1073/pnas.0508235103
18. Dorweiler, B., I. Grechowa, A. Wallrath, C.F. Vahl, and S. Horke. 2014. Activation of the proapoptotic unfolded protein response in plaques of the human carotid artery. Eur. J. Vasc. Endovasc. Surg. 48:248-257. http://dx.doi.org/10.1016/j.ejvs.2014.06.038
19. Drechsler, M., R. de Jong, J. Rossaint, J.R. Viola, G. Leoni, J.M. Wang, J. Grommes, R. Hinkel, C. Kupatt, C. Weber, et al. 2015. Annexin A1 counteracts chemokine-induced arterial myeloid cell recruitment. Circ. Res. 116:827-835. http://dx.doi.org/10.1161/CIRCRESAHA.116.305825
20. Duewell, P., H. Kono, K.J. Rayner, C.M. Sirois, G. Vladimer, F.G. Bauernfeind, G.S. Abela, L. Franchi, G. Nuñez, M. Schnurr, et al. 2010. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 464:1357-1361. http://dx.doi.org/10.1038/nature08938
21. Dunn, J., H. Qiu, S. Kim, D. Jjingo, R. Hoffman, C.W. Kim, I. Jang, D.J. Son, D. Kim, C. Pan, et al. 2014. Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis. J. Clin. Invest. 124:3187-3199. http://dx.doi.org/10.1172/JCI74792
22. Dutta, P., G. Courties, Y. Wei, F. Leuschner, R. Gorbatov, C.S. Robbins, Y. Iwamoto, B. Thompson, A.L. Carlson, T. Heidt, et al. 2012. Myocardial infarction accelerates atherosclerosis. Nature. 487:325-329. http://dx.doi.org/10.1038/nature11260
23. Falk, E., M. Nakano, J.F. Bentzon, A.V. Finn, and R. Virmani. 2013. Update on acute coronary syndromes: the pathologists' view. Eur. Heart J. 34:719-728. http://dx.doi.org/10.1093/eurheartj/ehs411
24. Fang, H., J. Lin, L. Wang, P. Xie, X. Wang, J. Fu, W. Ai, S. Chen, F. Chen, F. Zhang, et al. 2013. Kruppel-like factor 2 regulates dendritic cell activation in patients with acute coronary syndrome. Cell. Physiol. Biochem. 32:931-941. http://dx.doi.org/10.1159/000354496
25. Feaver, R.E., B.D. Gelfand, C. Wang, M.A. Schwartz, and B.R. Blackman. 2010. Atheroprone hemodynamics regulate fibronectin deposition to create positive feedback that sustains endothelial inflammation. Circ. Res. 106:1703-1711. http://dx.doi.org/10.1161/CIRCRESAHA.109.216283
26. Feil, S., B. Fehrenbacher, R. Lukowski, F. Essmann, K. Schulze-Osthoff, M. Schaller, and R. Feil. 2014. Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis. Circ. Res. 115:662-667. http://dx.doi.org/10.1161/CIRCRESAHA.115.304634
27. Fessler, M.B., and J.S. Parks. 2011. Intracellular lipid flux and membrane microdomains as organizing principles in inflammatory cell signaling. J. Immunol. 187:1529-1535. http://dx.doi.org/10.4049/jimmunol.1100253
28. Fredman, G., L. Ozcan, S. Spolitu, J. Hellmann, M. Spite, J. Backs, and I. Tabas 2014. Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B4 synthesis by inhibiting a calcium-activated kinase pathway. Proc. Natl. Acad. Sci. USA. 111:14530-14535. http://dx.doi.org/10.1073/pnas.1410851111
29. Fredman, G., N. Kamaly, S. Spolitu, J. Milton, D. Ghorpade, R. Chiasson, G. Kuriakose, M. Perretti, O. Farokzhad, and I. Tabas. 2015. Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice. Sci. Transl. Med. 7:275ra20. http://dx.doi.org/10.1126/scitranslmed.aaa1065
30. Garbin, U., E. Baggio, C. Stranieri, A. Pasini, S. Manfro, C. Mozzini, P. Vallerio, G. Lipari, F. Merigo, G. Guidi, et al. 2013. Expansion of necrotic core and shedding of Mertk receptor in human carotid plaques: a role for oxidized polyunsaturated fatty acids?. Cardiovasc. Res. 97:125-133. http://dx.doi.org/10.1093/cvr/cvs301
31. Gerrity, R.G., M. Richardson, J.B. Somer, F.P. Bell, and C.J. Schwartz. 1977. 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. 89:313-334.
32. Gimbrone, M.A., Jr., and G. García-Cardeña. 2013. Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis. Cardiovasc. Pathol 22:9-15. http://dx.doi.org/10.1016/j.carpath.2012.06.006
33. Glass, C.K., and J.L. Witztum. 2001. Atherosclerosis. the road ahead. Cell. 104:503-516. http://dx.doi.org/10.1016/S0092-8674(01)00238-0
34. Gomez, D., and G.K. Owens. 2012. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovasc. Res. 95:156-164. http://dx.doi.org/10.1093/cvr/cvs115
35. Gomez, D., L.S. Shankman, A.T. Nguyen, and G.K. Owens. 2013. Detection of histone modifications at specific gene loci in single cells in histological sections. Nat. Methods. 10:171-177. http://dx.doi.org/10.1038/nmeth.2332
36. Hajra, L., A.I. Evans, M. Chen, S.J. Hyduk, T. Collins, and M.I. Cybulsky. 2000. The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc. Natl. Acad. Sci. USA. 97:9052-9057. http://dx.doi.org/10.1073/pnas.97.16.9052
37. Haka, A.S., I. Grosheva, E. Chiang, A.R. Buxbaum, B.A. Baird, L.M. Pierini, and F.R. Maxfield. 2009. Macrophages create an acidic extracellular hydrolytic compartment to digest aggregated lipoproteins. Mol. Biol. Cell. 20:4932-4940. http://dx.doi.org/10.1091/mbc. E09-07-0559
38. Hansson, G.K., and A. Hermansson. 2011. The immune system in atherosclerosis. Nat. Immunol. 12:204-212. http://dx.doi.org/10.1038/ni.2001
39. Hansson, G.K., S. Chao, S.M. Schwartz, and M.A. Reidy. 1985. Aortic endothelial cell death and replication in normal and lipopolysaccharide-treated rats. Am. J. Pathol. 121:123-127.
40. Hochreiter-Hufford, A., and K.S. Ravichandran. 2013. Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion. Cold Spring Harb. Perspect Biol. 5:a008748. http://dx.doi.org/10.1101/cshperspect.a008748
41. Iwata, H., I. Manabe, K. Fujiu, T. Yamamoto, N. Takeda, K. Eguchi, A. Furuya, M. Kuro-o, M. Sata, and R. Nagai. 2010. Bone marrow-derived cells contribute to vascular inflammation but do not differentiate into smooth muscle cell lineages. Circulation. 122:2048-2057. http://dx.doi.org/10.1161/CIRCULATIONAHA.110.965202
42. Jiang, Y.Z., J.M. Jiménez, K. Ou, M.E. McCormick, L.D. Zhang, and P.F. Davies. 2014. Hemodynamic disturbed flow induces differential DNA methylation of endothelial Kruppel-Like Factor 4 promoter in vitro and in vivo. Circ. Res 115:32-43. http://dx.doi.org/10.1161/CIRCRESAHA.115.303883
43. Jung, B., H. Obinata, S. Galvani, K. Mendelson, B.S. Ding, A. Skoura, B. Kinzel, V. Brinkmann, S. Rafii, T. Evans, and T. Hla. 2012. Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development. Dev. Cell. 23:600-610. http://dx.doi.org/10.1016/j.devcel.2012.07.015
44. Kanters, E., M. Pasparakis, M.J. Gijbels, M.N. Vergouwe, I. Partouns-Hendriks, R.J. Fijneman, B.E. Clausen, I. Förster, M.M. Kockx, K. Rajewsky, et al. 2003. Inhibition of NF-kappaB activation in macrophages increases atherosclerosis in LDL receptor-deficient mice. J. Clin. Invest. 112:1176-1185. http://dx.doi.org/10.1172/JCI200318580
45. Koo, A., C.F. Dewey Jr., and G. García-Cardeña. 2013. Hemodynamic shear stress characteristic of atherosclerosis-resistant regions promotes glycocalyx formation in cultured endothelial cells. Am. J. Physiol. Cell Physiol. 304:C137-C146. http://dx.doi.org/10.1152/ajpcell.00187.2012
46. Kumar, S., C.W. Kim, R.D. Simmons, and H. Jo. 2014. Role of flow-sensitive microRNAs in endothelial dysfunction and atherosclerosis: mechanosensitive athero-miRs. Arterioscler. Thromb. Vasc. Biol. 34:2206-2216. http://dx.doi.org/10.1161/ATVBAHA.114.303425
47. Li, G., M. Mongillo, K.T. Chin, H. Harding, D. Ron, A.R. Marks, and I. Tabas. 2009. Role of ERO1-α-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J. Cell Biol. 186:783-792. http://dx.doi.org/10.1083/jcb.200904060
48. Li, J., B. Hou, S. Tumova, K. Muraki, A. Bruns, M.J. Ludlow, A. Sedo, A.J. Hyman, L. McKeown, R.S. Young, et al. 2014. Piezo1 integration of vascular architecture with physiological force. Nature. 515:279-282. http://dx.doi.org/10.1038/nature13701
49. Libby, P. 2008. The molecular mechanisms of the thrombotic complications of atherosclerosis. J. Intern. Med. 263:517-527. http://dx.doi.org/10.1111/j.1365-2796.2008.01965.x
50. Libby, P. 2013. Collagenases and cracks in the plaque. J. Clin. Invest. 123:3201-3203. http://dx.doi.org/10.1172/JCI67526
51. Libby, P., I. Tabas, G. Fredman, and E.A. Fisher. 2014. Inflammation and its resolution as determinants of acute coronary syndromes. Circ. Res. 114:1867-1879. http://dx.doi.org/10.1161/CIRCRESAHA.114.302699
52. Lin, J., H. Li, M. Yang, J. Ren, Z. Huang, F. Han, J. Huang, J. Ma, D. Zhang, Z. Zhang, et al. 2013. A role of RIP3-mediated macrophage necrosis in atherosclerosis development. Cell Reports. 3:200-210. http://dx.doi.org/10.1016/j.celrep.2012.12.012
53. Lingrel, J.B., R. Pilcher-Roberts, J.E. Basford, P. Manoharan, J. Neumann, E.S. Konaniah, R. Srinivasan, V.Y. Bogdanov, and D.Y. Hui. 2012. Myeloid-specific Krüppel-like factor 2 inactivation increases macrophage and neutrophil adhesion and promotes atherosclerosis. Circ. Res. 110:1294-1302. http://dx.doi.org/10.1161/CIRCRESAHA.112.267310
54. Liu, Y., C. Collins, W.B. Kiosses, A.M. Murray, M. Joshi, T.R. Shepherd, E.J. Fuentes, and E. Tzima. 2013. A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress. J. Cell Biol. 201:863-873. http://dx.doi.org/10.1083/jcb.201207115
55. Lu, X., and V. Kakkar. 2014. Inflammasome and atherogenesis. Curr. Pharm. Des 20:108-124. http://dx.doi.org/10.2174/13816128113199990586
56. Lusis, A.J. 2000. Atherosclerosis. Nature. 407:233-241. http://dx.doi.org/10.1038/35025203
57. Marin, T., B. Gongol, Z. Chen, B. Woo, S. Subramaniam, S. Chien, and J.Y. Shyy 2013. Mechanosensitive microRNAs-role in endothelial responses to shear stress and redox state. Free Radic. Biol. Med. 64:61-68. http://dx.doi.org/10.1016/j.freeradbiomed.2013.05.034
58. Martin, K., S. Weiss, P. Metharom, J. Schmeckpeper, B. Hynes, J. O'Sullivan, and N. Caplice. 2009. Thrombin stimulates smooth muscle cell differentiation from peripheral blood mononuclear cells via protease-activated receptor-1, RhoA, and myocardin. Circ. Res. 105:214-218. http://dx.doi.org/10.1161/CIRCRESAHA.109.199984
59. McGill, H.C., Jr., J.C. Geer, and R.L. Holman. 1957. Sites of vascular vulnerability in dogs demonstrated by Evans blue. AMA Arch. Pathol. 64:303-311.
60. Moore, K.J., and I. Tabas. 2011. Macrophages in the pathogenesis of atherosclerosis. Cell. 145:341-355. http://dx.doi.org/10.1016/j.cell.2011.04.005
61. Mullick, A.E., K. Soldau, W.B. Kiosses, T.A. Bell III, P.S. Tobias, and L.K. Curtiss 2008. Increased endothelial expression of Toll-like receptor 2 at sites of disturbed blood flow exacerbates early atherogenic events. J. Exp. Med 205:373-383. http://dx.doi.org/10.1084/jem.20071096
62. Murphy, A.J., D. Dragoljevic, and A.R. Tall. 2014. Cholesterol efflux pathways regulate myelopoiesis: a potential link to altered macrophage function in atherosclerosis. Front. Immunol. 5:490. http://dx.doi.org/10.3389/fimmu.2014.00490
63. Murphy, P.A., and R.O. Hynes. 2014. Alternative splicing of endothelial fibronectin is induced by disturbed hemodynamics and protects against hemorrhage of the vessel wall. Arterioscler. Thromb. Vasc. Biol. 34:2042-2050. http://dx.doi.org/10.1161/ATVBAHA.114.303879
64. Myoishi, M., H. Hao, T. Minamino, K. Watanabe, K. Nishihira, K. Hatakeyama, Y. Asada, K. Okada, H. Ishibashi-Ueda, G. Gabbiani, et al. 2007. Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome. Circulation. 116:1226-1233. http://dx.doi.org/10.1161/CIRCULATIONAHA.106.682054
65. Nathan, C., and A. Ding. 2010. Nonresolving inflammation. Cell. 140:871-882. http://dx.doi.org/10.1016/j.cell.2010.02.029
66. Ohnesorge, N., D. Viemann, N. Schmidt, T. Czymai, D. Spiering, M. Schmolke, S. Ludwig, J. Roth, M. Goebeler, and M. Schmidt. 2010. Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppellike factor 4 (KLF4). J. Biol. Chem. 285:26199-26210. http://dx.doi.org/10.1074/jbc. M110.103127
67. Pabbisetty, S.K., W. Rabacal, D. Maseda, D. Cendron, P.L. Collins, K.L. Hoek, V.V. Parekh, T.M. Aune, and E. Sebzda. 2014. KLF2 is a rate-limiting transcription factor that can be targeted to enhance regulatory T-cell production. Proc. Natl. Acad. Sci. USA. 111:9579-9584. http://dx.doi.org/10.1073/pnas.1323493111
68. Parmar, K.M., H.B. Larman, G. Dai, Y. Zhang, E.T. Wang, S.N. Moorthy, J.R. Kratz, Z. Lin, M.K. Jain, M.A. Gimbrone Jr., and G. García-Cardeña. 2006. Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J. Clin. Invest. 116:49-58. http://dx.doi.org/10.1172/JCI24787
69. Peled, M., and E.A. Fisher. 2014. Dynamic aspects of macrophage polarization during atherosclerosis progression and regression. Front. Immunol. 5:579. http://dx.doi.org/10.3389/fimmu.2014.00579
70. Ranade, S.S., Z. Qiu, S.H. Woo, S.S. Hur, S.E. Murthy, S.M. Cahalan, J. Xu, J. Mathur, M. Bandell, B. Coste, et al. 2014. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc. Natl. Acad. Sci USA. 111:10347-10352. http://dx.doi.org/10.1073/pnas.1409233111
71. Robbins, C.S., I. Hilgendorf, G.F. Weber, I. Theurl, Y. Iwamoto, J.L. Figueiredo, R. Gorbatov, G.K. Sukhova, L.M. Gerhardt, D. Smyth, et al. 2013. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat. Med. 19:1166-1172. http://dx.doi.org/10.1038/nm.3258
72. Rong, J.X., M. Shapiro, E. Trogan, and E.A. Fisher. 2003. Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading. Proc. Natl. Acad. Sci. USA. 100:13531-13536. http://dx.doi.org/10.1073/pnas.1735526100
73. Sakai, M., S. Kobori, A. Miyazaki, and S. Horiuchi. 2000. Macrophage proliferation in atherosclerosis. Curr. Opin. Lipidol. 11:503-509. http://dx.doi.org/10.1097/00041433-200010000-00008
74. Sather, S., K.D. Kenyon, J.B. Lefkowitz, X. Liang, B.C. Varnum, P.M. Henson, and D.K. Graham. 2007. A soluble form of the Mer receptor tyrosine kinase inhibits macrophage clearance of apoptotic cells and platelet aggregation. Blood. 109:1026-1033. http://dx.doi.org/10.1182/blood-2006-05-021634
75. Schrijvers, D.M., G.R. De Meyer, M.M. Kockx, A.G. Herman, and W. Martinet. 2005. Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 25:1256-1261. http://dx.doi.org/10.1161/01.ATV.0000166517.18801.a7
76. Sharma, N., Y. Lu, G. Zhou, X. Liao, P. Kapil, P. Anand, G.H. Mahabeleshwar, J.S. Stamler, and M.K. Jain. 2012. Myeloid Krüppel-like factor 4 deficiency augments atherogenesis in ApoE-/- mice-brief report. Arterioscler. Thromb Vasc. Biol. 32:2836-2838. http://dx.doi.org/10.1161/ATVBAHA.112.300471
77. Sheedy, F.J., A. Grebe, K.J. Rayner, P. Kalantari, B. Ramkhelawon, S.B. Carpenter, C.E. Becker, H.N. Ediriweera, A.E. Mullick, D.T. Golenbock, et al. 2013. CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat. Immunol. 14:812-820. http://dx.doi.org/10.1038/ni.2639
78. Spann, N.J., L.X. Garmire, J.G. McDonald, D.S. Myers, S.B. Milne, N. Shibata, D. Reichart, J.N. Fox, I. Shaked, D. Heudobler, et al. 2012. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell. 151:138-152. http://dx.doi.org/10.1016/j.cell.2012.06.054
79. Stewart, H.J., A.L. Guildford, D.J. Lawrence-Watt, and M. Santin. 2009. Substrate-induced phenotypical change of monocytes/macrophages into myofibroblast-like cells: a new insight into the mechanism of in-stent restenosis. J. Biomed. Mater. Res. A. 90A:465-471. http://dx.doi.org/10.1002/jbm.a.32100
80. Tabas, I. 2005. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency. Arterioscler. Thromb. Vasc. Biol. 25:2255-2264. http://dx.doi.org/10.1161/01.ATV.0000184783.04864.9f
81. Tabas, I. 2010. Macrophage death and defective inflammation resolution in atherosclerosis. Nat. Rev. Immunol. 10:36-46. http://dx.doi.org/10.1038/nri2675
82. Tabas, I., and C.K. Glass. 2013. Anti-inflammatory therapy in chronic disease: challenges and opportunities. Science. 339:166-172. http://dx.doi.org/10.1126/science.1230720
83. Tabas, I., and D. Ron. 2011. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat. Cell Biol. 13:184-190. http://dx.doi.org/10.1038/ncb0311-184
84. Tabas, I., K.J. Williams, and J. Borén. 2007. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 116:1832-1844. http://dx.doi.org/10.1161/CIRCULATIONAHA106.676890
85. Tacke, F., D. Alvarez, T.J. Kaplan, C. Jakubzick, R. Spanbroek, J. Llodra, A. Garin, J. Liu, M. Mack, N. van Rooijen, et al. 2007. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J. Clin. Invest. 117:185-194.
86. Takada, K., X. Wang, G.T. Hart, O.A. Odumade, M.A. Weinreich, K.A. Hogquist, and S.C. Jameson. 2011. Kruppel-like factor 2 is required for trafficking but not quiescence in postactivated T cells. J. Immunol. 186:775-783. http://dx.doi.org/10.4049/jimmunol.1000094
87. Thomas, J.A., R.A. Deaton, N.E. Hastings, Y. Shang, C.W. Moehle, U. Eriksson, S. Topouzis, B.R. Wamhoff, B.R. Blackman, and G.K. Owens. 2009. PDGF-DD, a novel mediator of smooth muscle cell phenotypic modulation, is upregulated in endothelial cells exposed to atherosclerosis-prone flow patterns. Am. J. Physiol. Heart Circ. Physiol. 296:H442-H452. http://dx.doi.org/10.1152/ajpheart.00165.2008
88. Thorp, E., G. Li, T.A. Seimon, G. Kuriakose, D. Ron, and I. Tabas. 2009. Reduced apoptosis and plaque necrosis in advanced atherosclerotic lesions of Apoe-/- and Ldlr-/- mice lacking CHOP. Cell Metab. 9:474-481. http://dx.doi.org/10.1016/j.cmet.2009.03.003
89. Thorp, E., M. Subramanian, and I. Tabas. 2011a. The role of macrophages and dendritic cells in the clearance of apoptotic cells in advanced atherosclerosis. Eur. J. Immunol. 41:2515-2518. http://dx.doi.org/10.1002/eji.201141719
90. Thorp, E., T. Vaisar, M. Subramanian, L. Mautner, C. Blobel, and I. Tabas. 2011b. Shedding of the Mer tyrosine kinase receptor is mediated by ADAM17 protein through a pathway involving reactive oxygen species, protein kinase Cδ, and p38 mitogen-activated protein kinase (MAPK). J. Biol. Chem 286:33335-33344. http://dx.doi.org/10.1074/jbc. M111.263020
91. Timmins, J.M., L. Ozcan, T.A. Seimon, G. Li, C. Malagelada, J. Backs, T. Backs, R. Bassel-Duby, E.N. Olson, M.E. Anderson, and I. Tabas. 2009. Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. J. Clin. Invest. 119:2925-2941. http://dx.doi.org/10.1172/JCI38857
92. van den Berg, B.M., J.A. Spaan, and H. Vink. 2009. Impaired glycocalyx barrier properties contribute to enhanced intimal low-density lipoprotein accumulation at the carotid artery bifurcation in mice. Pflugers Arch. 457:1199-1206. http://dx.doi.org/10.1007/s00424-008-0590-6
93. Vengrenyuk, Y., H. Nishi, X. Long, M. Ouimet, N. Savji, F.O. Martinez, C.P. Cassella, K.J. Moore, S.A. Ramsey, J.M. Miano, and E.A. Fisher. 2015. 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. 35:535-546. http://dx.doi.org/10.1161/ATVBAHA.114.304029
94. Villarreal, G., Jr., Y. Zhang, H.B. Larman, J. Gracia-Sancho, A. Koo, and G. García-Cardeña. 2010. Defining the regulation of KLF4 expression and its downstream transcriptional targets in vascular endothelial cells. Biochem. Biophys. Res. Commun. 391:984-989. http://dx.doi.org/10.1016/j.bbrc.2009.12.002
95. Virmani, R., A.P. Burke, F.D. Kolodgie, and A. Farb. 2002. Vulnerable plaque: the pathology of unstable coronary lesions. J. Interv. Cardiol. 15:439-446. http://dx.doi.org/10.1111/j.1540-8183.2002.tb01087.x
96. Wamhoff, B.R., M.H. Hoofnagle, A. Burns, S. Sinha, O.G. McDonald, and G.K. Owens 2004. A G/C element mediates repression of the SM22α promoter within phenotypically modulated smooth muscle cells in experimental atherosclerosis. Circ. Res. 95:981-988. http://dx.doi.org/10.1161/01.RES.0000147961.09840.fb
97. Wang, Y., G.Z. Wang, P.S. Rabinovitch, and I. Tabas. 2014. Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-κB-mediated inflammation in macrophages. Circ. Res. 114:421-433. http://dx.doi.org/10.1161/CIRCRESAHA.114.302153
98. Westerterp, M., A.E. Bochem, L. Yvan-Charvet, A.J. Murphy, N. Wang, and A.R. Tall. 2014. ATP-binding cassette transporters, atherosclerosis, and inflammation. Circ. Res. 114:157-170. http://dx.doi.org/10.1161/CIRCRESAHA.114.300738
99. Williams, K.J., and I. Tabas. 1995. The response-to-retention hypothesis of early atherogenesis. Arterioscler. Thromb. Vasc. Biol. 15:551-561. http://dx.doi.org/10.1161/01.ATV.15.5.551
100. Won, D., S.N. Zhu, M. Chen, A.M. Teichert, J.E. Fish, C.C. Matouk, M. Bonert, M. Ojha, P.A. Marsden, and M.I. Cybulsky. 2007. 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. 171:1691-1704. http://dx.doi.org/10.2353/ajpath.2007.060860
101. World Health Organization. 2014. The top 10 causes of death. Available at: http://www.who.int/mediacentre/factsheets/fs310/en/(accessed March 26, 2015)
102. Yoshida, T., K.H. Kaestner, and G.K. Owens. 2008. Conditional deletion of Krüppel-like factor 4 delays downregulation of smooth muscle cell differentiation markers but accelerates neointimal formation following vascular injury. Circ. Res. 102:1548-1557. http://dx.doi.org/10.1161/CIRCRESAHA108.176974
103. Zeng, L., A. Zampetaki, A. Margariti, A.E. Pepe, S. Alam, D. Martin, Q. Xiao, W. Wang, Z.G. Jin, G. Cockerill, et al. 2009. Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow. Proc. Natl. Acad. Sci. USA. 106:8326-8331. http://dx.doi.org/10.1073/pnas.0903197106
104. Zhou, G., A. Hamik, L. Nayak, H. Tian, H. Shi, Y. Lu, N. Sharma, X. Liao, A. Hale, L. Boerboom, et al. 2012. Endothelial Kruppel-like factor 4 protects against atherothrombosis in mice. J. Clin. Invest. 122:4727-4731. http://dx.doi.org/10.1172/JCI66056
105. Zhou, J., Y.S. Li, and S. Chien. 2014a. Shear stress-initiated signaling and its regulation of endothelial function. Arterioscler. Thromb. Vasc. Biol. 34:2191-2198. http://dx.doi.org/10.1161/ATVBAHA.114.303422
106. Zhou, J., Y.S. Li, K.C. Wang, and S. Chien. 2014b. Epigenetic mechanism in regulation of endothelial function by disturbed flow: Induction of DNA hypermethylation by DNMT1. Cell Mol Bioeng. 7:218-224. http://dx.doi.org/10.1007/s12195-014-0325-z
107. Zhou, R., A.S. Yazdi, P. Menu, and J. Tschopp. 2011. A role for mitochondria in NLRP3 inflammasome activation. Nature. 469:221-225. http://dx.doi.org/10.1038/nature09663