Reactive oxygen species and thiol redox signaling in the macrophage biology of atherosclerosis

Antioxidants and Redox Signaling

Volumn 17, Issue 12, 2012, Pages 1785-1795

  Tavakoli, Sina ^a   Asmis, Reto ^a,b  

^a UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^b University of Texas Health Science Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HYDROGEN PEROXIDE; HYDROXYL RADICAL; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; THIOL;

ATHEROGENESIS; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; CELL ACTIVATION; CELL DEATH; CELL DIFFERENTIATION; CHRONIC INFLAMMATION; CYTOLOGY; ENDOPLASMIC RETICULUM STRESS; FOAM CELL; HEART INFARCTION; HUMAN; MACROPHAGE; MACROPHAGE FUNCTION; MONOCYTE; NONHUMAN; OXIDATION REDUCTION REACTION; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; ATHEROSCLEROSIS; HUMANS; MACROPHAGES; OXIDATION-REDUCTION; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION;

EID: 84867713844     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2012.4638     Document Type: Review

References (86)

1. Alcouffe J, Caspar-Bauguil S, Garcia V, Salvayre R, Thomsen M, and Benoist H. Oxidized low density lipoproteins induce apoptosis in PHA-activated peripheral blood mononuclear cells and in the Jurkat T-cell line. J Lipid Res 40: 1200-1210, 1999.. (Pubitemid 29328523)
2. Asmis R and Begley JG. Oxidized LDL promotes peroxidemediated mitochondrial dysfunction and cell death in human macrophages: a caspase-3-independent pathway. Circ Res 92: e20-e29, 2003..
3. Asmis R, Begley JG, Jelk J, and Everson WV. Lipoprotein aggregation protects human monocyte-derived macrophages from OxLDL-induced cytotoxicity. J Lipid Res 46: 1124-1132, 2005.. (Pubitemid 43109828)
4. Asmis R and Jelk J. Vitamin E supplementation of human macrophages prevents neither foam cell formation nor increased susceptibility of foam cells to lysis by oxidized LDL. Arterioscler Thromb Vasc Biol 20: 2078-2086, 2000..
5. Balce DR, Li B, Allan ER, Rybicka JM, Krohn RM, and Yates RM. Alternative activation of macrophages by IL-4 enhances the proteolytic capacity of their phagosomes through syn-ergistic mechanisms. Blood 118: 4199-4208, 2011..
6. Bhatia VK, Yun S, Leung V, Grimsditch DC, Benson GM, Botto MB, Boyle JJ, and Haskard DO. Complement C1q reduces early atherosclerosis in low-density lipoprotein receptor-deficient mice. Am J Pathol 170: 416-426, 2007.. (Pubitemid 47339218)
7. Boullier A, Li Y, Quehenberger O, Palinski W, Tabas I, Witztum JL, and Miller YI. Minimally oxidized LDL offsets the apoptotic effects of extensively oxidized LDL and free cholesterol in macrophages. Arterioscler Thromb Vasc Biol 26: 1169-1176, 2006.. (Pubitemid 43732129)
8. Brys L, Beschin A, Raes G, Ghassabeh GH, Noel W, Brandt J, Brombacher F, and De Baetselier P. Reactive oxygen species and 12/15-lipoxygenase contribute to the antiproliferative capacity of alternatively activated myeloid cells elicited during helminth infection. J Immunol 174: 6095-6104, 2005.. (Pubitemid 40663798)
9. Callegari A, Liu Y, White CC, Chait A, Gough P, Raines EW, Cox D, Kavanagh TJ, and Rosenfeld ME. Gain and loss of function for glutathione synthesis: impact on advanced atherosclerosis in apolipoprotein E-deficient mice. Arter-ioscler Thromb Vasc Biol 31: 2473-2482, 2011..
10. Clare K, Hardwick SJ, Carpenter KL, Weeratunge N, and Mitchinson MJ. Toxicity of oxysterols to human monocyte-macrophages. Atherosclerosis 118: 67-75, 1995..
11. Combadiere C, Potteaux S, Rodero M, Simon T, Pezard A, Esposito B, Merval R, Proudfoot A, Tedgui A, and Mallat Z. Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice. Circulation 117: 1649-1657, 2008.. (Pubitemid 351482605)
12. Devries-Seimon T, Li Y, Yao PM, Stone E, Wang Y, Davis RJ, Flavell R, and Tabas I. Cholesterol-induced macrophage apoptosis requires ER stress pathways and engagement of the type A scavenger receptor. J Cell Biol 171: 61-73, 2005.. (Pubitemid 41434602)
13. Dickhout JG, Hossain GS, Pozza LM, Zhou J, Lhotak S, and Austin RC. Peroxynitrite causes endoplasmic reticulum stress and apoptosis in human vascular endothelium: implications in atherogenesis. Arterioscler Thromb Vasc Biol 25: 2623-2629, 2005.. (Pubitemid 43732288)
14. Dickhout JG, Sood SK, and Austin RC. Role of endoplas-mic reticulum calcium disequilibria in the mechanism of homocysteine-induced ER stress. Antioxid Redox Signal 9: 1863-1873, 2007.. (Pubitemid 47622350)
15. Feng B, Yao PM, Li Y, Devlin CM, Zhang D, Harding HP, Sweeney M, Rong JX, Kuriakose G, Fisher EA, Marks AR, Ron D, and Tabas I. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 5: 781-792, 2003.. (Pubitemid 37087166)
16. Fernandez-Boyanapalli RF, Frasch SC, McPhillips K, Vandivier RW, Harry BL, Riches DW, Henson PM, and Bratton DL. Impaired apoptotic cell clearance in CGD due to altered macrophage programming is reversed by phosphatidylserine- dependent production of IL-4. Blood 113: 2047-2055, 2009..
17. Fu S, Yang L, Li P, Hofmann O, Dicker L, Hide W, Lin X, Watkins SM, Ivanov AR, and Hotamisligil GS. Aberrant li-pid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 473: 528-531, 2011..
18. Galle J, Hansen-Hagge T, Wanner C, and Seibold S. Impact of oxidized low density lipoprotein on vascular cells. Atherosclerosis 185: 219-226, 2006..
19. Gautier EL, Huby T, Witztum JL, Ouzilleau B, Miller ER, Saint-Charles F, Aucouturier P, Chapman MJ, and Lesnik P. Macrophage apoptosis exerts divergent effects on ath-erogenesis as a function of lesion stage. Circulation 119: 1795-1804, 2009..
20. Gilmore WJ and Kirby GM. Endoplasmic reticulum stress due to altered cellular redox status positively regulates murine hepatic CYP2A5 expression. J Pharmacol Exp Ther 308: 600-608, 2004.. (Pubitemid 38134222)
21. Heinloth A, Heermeier K, Raff U, Wanner C, and Galle J. Stimulation of NADPH oxidase by oxidized low-density lipoprotein induces proliferation of human vascular endo-thelial cells. J Am Soc Nephrol 11: 1819-1825, 2000..
22. Hessler JR, Robertson AL, Jr., and Chisolm GM, 3rd. LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture. Atherosclerosis 32: 213-229, 1979.. (Pubitemid 9129780)
23. Hiura TS, Li N, Kaplan R, Horwitz M, Seagrave JC, and Nel AE. The role of a mitochondrial pathway in the induction of apoptosis by chemicals extracted from diesel exhaust particles. J Immunol 165: 2703-2711, 2000.. (Pubitemid 30660720)
24. Imanishi T, Ikejima H, Tsujioka H, Kuroi A, Ishibashi K, Komukai K, Tanimoto T, Ino Y, Takeshita T, and Akasaka T. Association of monocyte subset counts with coronary fibrous cap thickness in patients with unstable angina pec-toris. Atherosclerosis 212: 628-635, 2010..
25. Ingersoll MA, Spanbroek R, Lottaz C, Gautier EL, Frankenberger M, Hoffmann R, Lang R, Haniffa M, Collin M, Tacke F, Habenicht AJ, Ziegler-Heitbrock L, and Randolph GJ. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 115: e10-e19, 2010..
26. Johnsen SH, Fosse E, Joakimsen O, Mathiesen EB, Stensland-Bugge E, Njolstad I, and Arnesen E. Monocyte count is a predictor of novel plaque formation: a 7-year follow-up study of 2610 persons without carotid plaque at baseline the Tromso Study. Stroke 36: 715-719, 2005..
27. Kaneko H, Anzai T, Horiuchi K, Kohno T, Nagai T, Anzai A, Takahashi T, Sasaki A, Shimoda M, Maekawa Y, Shimizu H, Yoshikawa T, Okada Y, Yozu R, and Fukuda K. Tumor necrosis factor-alpha converting enzyme is a key mediator of abdominal aortic aneurysm development. Atherosclerosis 218: 470-478, 2011..
28. Kaneko H, Anzai T, Morisawa M, Kohno T, Nagai T, Anzai A, Takahashi T, Shimoda M, Sasaki A, Maekawa Y, Yoshi-mura K, Aoki H, Tsubota K, Yoshikawa T, Okada Y, Ogawa S, and Fukuda K. Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization. Atherosclerosis 217: 350-357, 2011..
29. Khallou-Laschet J, Varthaman A, Fornasa G, Compain C, Gaston AT, Clement M, Dussiot M, Levillain O, Graff-Dubois S, Nicoletti A, and Caligiuri G. Macrophage plasticity in experimental atherosclerosis. PLoS One 5: e8852, 2010..
30. Khan MI, Pichna BA, Shi Y, Bowes AJ, and Werstuck GH. Evidence supporting a role for endoplasmic reticulum stress in the development of atherosclerosis in a hyperglycaemic mouse model. Antioxid Redox Signal 11: 2289-2298, 2009..
31. Kugiyama K, Sugiyama S, Ogata N, Oka H, Doi H, Ota Y, and Yasue H. Burst production of superoxide anion in human endothelial cells by lysophosphatidylcholine. Atherosclerosis 143: 201-204, 1999.. (Pubitemid 29138719)
32. Lee CF, Qiao M, Schroder K, Zhao Q, and Asmis R. Nox4 is a novel inducible source of reactive oxygen species in monocytes and macrophages and mediates oxidized low density lipoprotein-induced macrophage death. Circ Res 106: 1489-1497, 2010..
33. Li AC and Glass CK. The macrophage foam cell as a target for therapeutic intervention. Nat Med 8: 1235-1242, 2002.. (Pubitemid 35373554)
34. Li G, Scull C, Ozcan L, and Tabas I. NADPH oxidase links endoplasmic reticulum stress, oxidative stress, and PKR activation to induce apoptosis. J Cell Biol 191: 1113-1125, 2010..
35. Libby P. Inflammation in atherosclerosis. Nature 420: 868-874, 2002.. (Pubitemid 36019640)
36. Malhotra JD and Kaufman RJ. Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal 9: 2277-2293, 2007.. (Pubitemid 350059010)
37. Malhotra JD and Kaufman RJ. The endoplasmic reticulum and the unfolded protein response. Semin Cell Dev Biol 18: 716-731, 2007.. (Pubitemid 350138453)
38. Malhotra JD, Miao H, Zhang K, Wolfson A, Pennathur S, Pipe SW, and Kaufman RJ. Antioxidants reduce endoplas-mic reticulum stress and improve protein secretion. Proc Natl Acad Sci U S A 105: 18525-18530, 2008..
39. Mantovani A, Sica A, and Locati M. New vistas on macrophage differentiation and activation. Eur J Immunol 37: 14-16, 2007.. (Pubitemid 46128780)
40. Martinet W and De Meyer GR. Autophagy in atherosclerosis: a cell survival and death phenomenon with therapeutic potential. Circ Res 104: 304-317, 2009..
41. McMillen TS, Heinecke JW, and LeBoeuf RC. Expression of human myeloperoxidase by macrophages promotes atherosclerosis in mice. Circulation 111: 2798-2804, 2005.. (Pubitemid 40791552)
42. McPhillips K, Janssen WJ, Ghosh M, Byrne A, Gardai S, Remigio L, Bratton DL, Kang JL, and Henson P. TNF-alpha inhibits macrophage clearance of apoptotic cells via cytosolic phospholipase A2 and oxidant-dependent mechanisms. J Immunol 178: 8117-8126, 2007.. (Pubitemid 46898084)
43. Myoishi M, Hao H, Minamino T, Watanabe K, Nishihira K, Hatakeyama K, Asada Y, Okada K, Ishibashi-Ueda H, Gabbiani G, Bochaton-Piallat ML, Mochizuki N, and Kita-kaze M. Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome. Circulation 116: 1226-1233, 2007.. (Pubitemid 47517533)
44. Nahrendorf M, Jaffer FA, Kelly KA, Sosnovik DE, Aikawa E, Libby P, and Weissleder R. Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 114: 1504-1511, 2006.. (Pubitemid 44527006)
45. Nasir K, Guallar E, Navas-Acien A, Criqui MH, and Lima JA. Relationship of monocyte count and peripheral arterial disease: results from the National Health and Nutrition Examination Survey 1999-2002. Arterioscler Thromb Vasc Biol 25: 1966-1971, 2005.. (Pubitemid 41243470)
46. Ohara Y, Peterson TE, Zheng B, Kuo JF, and Harrison DG. Lysophosphatidylcholine increases vascular superoxide an-ion production via protein kinase C activation. Arterioscler Thromb 14: 1007-1013, 1994..
47. Oorni K, Pentikainen MO, Ala-Korpela M, and Kovanen PT. Aggregation, fusion, and vesicle formation of modified low density lipoprotein particles: molecular mechanisms and effects on matrix interactions. J Lipid Res 41: 1703-1714, 2000..
48. Ouimet M, Franklin V, Mak E, Liao X, Tabas I, and Marcel YL. Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. Cell Metab 13: 655-667, 2011..
49. Outinen PA, Sood SK, Pfeifer SI, Pamidi S, Podor TJ, Li J, Weitz JI, and Austin RC. Homocysteine-induced endoplas-mic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells. Blood 94: 959-967, 1999.. (Pubitemid 29361827)
50. Pacher P, Beckman JS, and Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87: 315-424, 2007.. (Pubitemid 46217686)
51. Parathath S, Grauer L, Huang LS, Sanson M, Distel E, Goldberg IJ, and Fisher EA. Diabetes adversely affects macrophages during atherosclerotic plaque regression in mice. Diabetes 60: 1759-1769, 2011..
52. Park CH, Kim MR, Han JM, Jeong TS, and Sok DE. Lyso-phosphatidylcholine exhibits selective cytotoxicity, accompanied by ROS formation, in RAW 264.7 macrophages. Lipids 44: 425-435, 2009..
53. Parthasarathy S. Oxidation of low-density lipoprotein by thiol compounds leads to its recognition by the acetyl LDL receptor. Biochim Biophys Acta 917: 337-340, 1987.. (Pubitemid 17004984)
54. Pelegrin P and Surprenant A. Dynamics of macrophage polarization reveal new mechanism to inhibit IL-1beta release through pyrophosphates. EMBO J 28: 2114-2127, 2009..
55. Podrez EA, Febbraio M, Sheibani N, Schmitt D, Silverstein RL, Hajjar DP, Cohen PA, Frazier WA, Hoff HF, and Hazen SL. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. J Clin Invest 105: 1095-1108, 2000.. (Pubitemid 30217694)
56. Qiao M, Kisgati M, Cholewa JM, Zhu W, Smart EJ, Sulistio MS, and Asmis R. Increased expression of glutathione re-ductase in macrophages decreases atherosclerotic lesion formation in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol 27: 1375-1382, 2007.. (Pubitemid 46809428)
57. Qiao M, Zhao Q, Lee CF, Tannock LR, Smart EJ, LeBaron RG, Phelix CF, Rangel Y, and Asmis R. Thiol oxidative stress induced by metabolic disorders amplifies macrophage chemotactic responses and accelerates atherogenesis and kidney injury in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 29: 1779-1786, 2009..
58. Rabbani R and Topol EJ. Strategies to achieve coronary arterial plaque stabilization. Cardiovasc Res 41: 402-417, 1999.. (Pubitemid 29087337)
59. Reid VC and Mitchinson MJ. Toxicity of oxidised low density lipoprotein towards mouse peritoneal macrophages in vitro. Atherosclerosis 98: 17-24, 1993.. (Pubitemid 23010420)
60. Rueckschloss U, Galle J, Holtz J, Zerkowski HR, and Mor-awietz H. Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy. Circulation 104: 1767-1772, 2001.. (Pubitemid 32963340)
61. Scherz-Shouval R and Elazar Z. Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci 36: 30-38, 2011..
62. Schrijvers DM, De Meyer GR, and Martinet W. Autophagy in atherosclerosis: a potential drug target for plaque stabilization. Arterioscler Thromb Vasc Biol 31: 2787-2791, 2011..
63. Seimon TA, Nadolski MJ, Liao X, Magallon J, Nguyen M, Feric NT, Koschinsky ML, Harkewicz R, Witztum JL, Tsimikas S, Golenbock D, Moore KJ, and Tabas I. Athero-genic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticu-lum stress. Cell Metab 12: 467-482, 2010..
64. Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, and Miyata M. Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apoli-poprotein E. Proc Natl Acad Sci U S A 92: 8264-8268, 1995..
65. Stoneman V, Braganza D, Figg N, Mercer J, Lang R, God-dard M, and Bennett M. Monocyte/macrophage suppression in CD11b diphtheria toxin receptor transgenic mice differentially affects atherogenesis and established plaques. Circ Res 100: 884-893, 2007.. (Pubitemid 46555694)
66. Sugamura K and Keaney JF, Jr. Reactive oxygen species in cardiovascular disease. Free Radic Biol Med 51: 978-992, 2011..
67. Swirski FK, Weissleder R, and Pittet MJ. Heterogeneous in vivo behavior of monocyte subsets in atherosclerosis. Arterioscler Thromb Vasc Biol 29: 1424-1432, 2009..
68. Tabas I. Consequences of cellular cholesterol accumulation: basic concepts and physiological implications. J Clin Invest 110: 905-911, 2002..
69. Tabas I. Macrophage apoptosis in atherosclerosis: consequences on plaque progression and the role of endoplasmic reticulum stress. Antioxid Redox Signal 11: 2333-2339, 2009..
70. Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol 10: 36-46, 2010..
71. Takao S, Smith EH, Wang D, Chan CK, Bulkley GB, and Klein AS. Role of reactive oxygen metabolites in murine peritoneal macrophage phagocytosis and phagocytic killing. Am J Physiol 271: C1278-C1284, 1996..
72. Tavakoli S and Sadeghi MM. Imaging of vascular biology in the heart. Curr Cardiovasc Imaging Rep 2: 40-49, 2009..
73. -/- mice lacking CHOP. Cell Metab 9: 474-481, 2009..
74. Thorp E and Tabas I. Mechanisms and consequences of efferocytosis in advanced atherosclerosis. J Leukoc Biol 86: 1089-1095, 2009..
75. Tsukano H, Gotoh T, Endo M, Miyata K, Tazume H, Ka-domatsu T, Yano M, Iwawaki T, Kohno K, Araki K, Mizuta H, and Oike Y. The endoplasmic reticulum stress-C/EBP homologous protein pathway-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques. Arterioscler Thromb Vasc Biol 30: 1925-1932, 2010..
76. Ullevig S, Zhao Q, Lee CF, Kim HS, Zamora D, and Asmis R. NADPH oxidase 4 mediates monocyte priming and accelerated chemotaxis induced by metabolic stress. Arterioscler Thromb Vasc Biol 32: 415-426, 2012..
77. Violi F, Basili S, Nigro C, and Pignatelli P. Role of NADPH oxidase in atherosclerosis. Future Cardiol 5: 83-92, 2009..
78. Waldo SW, Li Y, Buono C, Zhao B, Billings EM, Chang J, and Kruth HS. Heterogeneity of human macrophages in culture and in atherosclerotic plaques. Am J Pathol 172: 1112-1126, 2008.. (Pubitemid 351520007)
79. Wang Y, Qiao M, Mieyal JJ, Asmis LM, and Asmis R. Molecular mechanism of glutathione-mediated protection from oxidized low-density lipoprotein-induced cell injury in human macrophages: role of glutathione reductase and glu-taredoxin. Free Radic Biol Med 41: 775-785, 2006.. (Pubitemid 44163413)
80. Wildgruber M, Lee H, Chudnovskiy A, Yoon TJ, Etzrodt M, Pittet MJ, Nahrendorf M, Croce K, Libby P, Weissleder R, and Swirski FK. Monocyte subset dynamics in human atherosclerosis can be profiled with magnetic nano-sensors. PLoS One 4: e5663, 2009..
81. Yakubenko VP, Bhattacharjee A, Pluskota E, and Cathcart MK. AlphaMbeta integrin activation prevents alternative activation of human and murine macrophages and impedes foam cell formation. Circ Res 108: 544-554, 2011..
82. Yao PM and Tabas I. Free cholesterol loading of macrophages induces apoptosis involving the fas pathway. J Biol Chem 275: 23807-23813, 2000.. (Pubitemid 30624666)
83. Yla-Herttuala S, Palinski W, Rosenfeld ME, Parthasarathy S, Carew TE, Butler S, Witztum JL, and Steinberg D. Evidence for the presence of oxidatively modified low density lipo-protein in atherosclerotic lesions of rabbit and man. J Clin Invest 84: 1086-1095, 1989.. (Pubitemid 19247577)
84. Zhang D, Jiang X, Fang P, Yan Y, Song J, Gupta S, Schafer AI, Durante W, Kruger WD, Yang X, and Wang H. Hy-perhomocysteinemia promotes inflammatory monocyte generation and accelerates atherosclerosis in transgenic cy-stathionine beta-synthase-deficient mice. Circulation 120: 1893-1902, 2009..
85. Zhaorigetu S, Yang Z, Toma I, McCaffrey TA, and Hu CA. Apolipoprotein L6, induced in atherosclerotic lesions, promotes apoptosis and blocks Beclin 1-dependent autophagy in atherosclerotic cells. J Biol Chem 286: 27389-27398, 2011..
86. Zhou J, Lhotak S, Hilditch BA, and Austin RC. Activation of the unfolded protein response occurs at all stages of atherosclerotic lesion development in apolipoprotein E-deficient mice. Circulation 111: 1814-1821, 2005.. (Pubitemid 40525147)