Skip to main content
SpringerLink
Log in

The UPR in atherosclerosis

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Multiple systemic factors and local stressors in the arterial wall can disturb the functions of endoplasmic reticulum (ER), causing ER stress in endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages during the initiation and progression of atherosclerosis. As a protective response to restore ER homeostasis, the unfolded protein response (UPR) is initiated by three major ER sensors: protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α), and activating transcription factor 6 (ATF6). The activation of the various UPR signaling pathways displays a temporal pattern of activation at different stages of the disease. The ATF6 and IRE1α pathways that promote the expression of protein chaperones in ER are activated in ECs in athero-susceptible regions of pre-lesional arteries and before the appearance of foam cells. The PERK pathway that reduces ER protein client load by blocking protein translation is activated in SMCs and macrophages in early lesions. The activation of these UPR signaling pathways aims to cope with the ER stress and plays a pro-survival role in the early stage of atherosclerosis. However, with the progression of atherosclerosis, the extended duration and increased intensity of ER stress in lesions lead to prolonged and enhanced UPR signaling. Under this circumstance, the PERK pathway induces expression of death effectors, and possibly IRE1α activates apoptosis signaling pathways, leading to apoptosis of macrophages and SMCs in advanced lesions. Importantly, UPR-mediated cell death is associated with plaque instability and the clinical progression of atherosclerosis. Moreover, UPR signaling is linked to inflammation and possibly to macrophage differentiation in lesions. Therapeutic approaches targeting the UPR may have promise in the prevention and/or regression of atherosclerosis. However, more progress is needed to fully understand all of the roles of the UPR in atherosclerosis and to harness this information for therapeutic advances.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

Ampkα2:

AMP-activated protein kinase alpha 2

AP1:

Activator protein 1

apoB:

Apolipoprotein-B

ATF6:

Activating transcription factor 6

BFA:

Brefeldin A

CaMKII:

Calcium/calmodulin-dependent protein kinase II

CASP2:

Caspase-2

CHOP:

CCAAT/enhancer binding protein homologous protein

CXCL3:

Chemokine CXC motif ligand 3

DCA:

Directional coronary atherectomy

ECs:

Endothelial cells

eIF2α:

Eukaryotic initiation factor 2α

ER:

Endoplasmic reticulum

ERAD:

ER-associated degradation

ERK:

Extracellular signal-regulated kinase

ERO1α:

ER oxidase 1α

FC:

Free cholesterol

GRP78:

Glucose-regulated protein 78

HHcy:

Hyperhomocysteinemia

HSP47:

Heat shock protein 47

HUVEC:

Human umbilical vein endothelial cell

IKK:

IκB kinase

IL-6:

Interleukin-6

IRE1α:

Inositol-requiring protein 1 α

JNK:

c-Jun-N-terminal kinase

LXR:

Liver X receptor

MAPK:

Mitogen-activated protein kinases

M-CSF:

Macrophage colony-stimulating factor

NLRP3:

Nucleotide oligomerization domain receptor protein 3

oxLDL:

Oxidized low-density lipoprotein

PBA:

4-Phenylbutyric acid

PERK:

Protein kinase RNA-like ER kinase

PP1c:

Protein phospholipase 1, catalytic subunit

PRRs:

Pattern recognition receptors

RIDD:

IRE1-dependent decay

SAP:

Stable angina pectoris

SMCs:

Smooth muscle cells

SRA1:

Steroid receptor RNA activator 1

STAT1:

Signal transducer and activator of transcription-1

sXBP1:

Spliced XBP1 protein

TDAG51:

T cell death associated gene 51

tHcy:

Total serum homocysteine

TLRs:

Toll-like receptors

TRAF2:

TNFR-associated factor 2

TNFα:

Tumor necrosis factor-α

TUDCA:

Tauroursodeoxycholic acid

TXNIP:

Thioredoxin-interacting protein

UPR:

Unfolded protein response

XBP1:

X-box binding protein 1

UAP:

Unstable angina pectoris

References

  1. Murray CJ, Lopez AD (1997) Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 349(9063):1436–1442

    PubMed  CAS  Google Scholar 

  2. Rader DJ, Daugherty A (2008) Translating molecular discoveries into new therapies for atherosclerosis. Nature 451(7181):904–913

    PubMed  CAS  Google Scholar 

  3. Tabas I (2010) The role of endoplasmic reticulum stress in the progression of atherosclerosis. Circ Res 107(7):839–850

    PubMed  CAS  Google Scholar 

  4. Minamino T, Komuro I, Kitakaze M (2010) Endoplasmic reticulum stress as a therapeutic target in cardiovascular disease. Circ Res 107(9):1071–1082

    PubMed  CAS  Google Scholar 

  5. Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8(7):519–529

    PubMed  CAS  Google Scholar 

  6. Szegezdi E et al (2006) Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 7(9):880–885

    PubMed  CAS  Google Scholar 

  7. Hetz C (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 13(2):89–102

    PubMed  CAS  Google Scholar 

  8. Williams KJ, Tabas I (1998) The response-to-retention hypothesis of atherogenesis reinforced. Curr Opin Lipidol 9(5):471–474

    PubMed  CAS  Google Scholar 

  9. Tabas I, Williams KJ, Boren J (2007) Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 116(16):1832–1844

    PubMed  CAS  Google Scholar 

  10. Doran AC, Meller N, McNamara CA (2008) Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler Thromb Vasc Biol 28(5):812–819

    PubMed  CAS  Google Scholar 

  11. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352(16):1685–1695

    PubMed  CAS  Google Scholar 

  12. Fuster V (1994) Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. Circulation 90(4):2126–2146

    PubMed  CAS  Google Scholar 

  13. 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(11):2255–2264

    PubMed  CAS  Google Scholar 

  14. Bennett MR (1999) Apoptosis of vascular smooth muscle cells in vascular remodelling and atherosclerotic plaque rupture. Cardiovasc Res 41(2):361–368

    PubMed  CAS  Google Scholar 

  15. Rutkowski DT, Hegde RS (2010) Regulation of basal cellular physiology by the homeostatic unfolded protein response. J Cell Biol 189(5):783–794

    PubMed  CAS  Google Scholar 

  16. Myoishi M et al (2007) Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome. Circulation 116(11):1226–1233

    PubMed  Google Scholar 

  17. Zhou J et al (2005) Activation of the unfolded protein response occurs at all stages of atherosclerotic lesion development in apolipoprotein E-deficient mice. Circulation 111(14):1814–1821

    PubMed  CAS  Google Scholar 

  18. Thorp E et al (2009) Reduced apoptosis and plaque necrosis in advanced atherosclerotic lesions of Apoe−/− and Ldlr−/− mice lacking CHOP. Cell Metab 9(5):474–481

    PubMed  CAS  Google Scholar 

  19. Hossain GS et al (2003) TDAG51 is induced by homocysteine, promotes detachment-mediated programmed cell death, and contributes to the development of atherosclerosis in hyperhomocysteinemia. J Biol Chem 278(32):30317–30327

    PubMed  CAS  Google Scholar 

  20. Maxfield FR, Tabas I (2005) Role of cholesterol and lipid organization in disease. Nature 438(7068):612–621

    PubMed  CAS  Google Scholar 

  21. Li Y et al (2004) Enrichment of endoplasmic reticulum with cholesterol inhibits sarcoplasmic-endoplasmic reticulum calcium ATPase-2b activity in parallel with increased order of membrane lipids: implications for depletion of endoplasmic reticulum calcium stores and apoptosis in cholesterol-loaded macrophages. J Biol Chem 279(35):37030–37039

    PubMed  CAS  Google Scholar 

  22. Fu Y, Luo N, Lopes-Virella MF (2000) Oxidized LDL induces the expression of ALBP/aP2 mRNA and protein in human THP-1 macrophages. J Lipid Res 41(12):2017–2023

    PubMed  CAS  Google Scholar 

  23. Erbay E et al (2009) Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Nat Med 15(12):1383–1391

    PubMed  CAS  Google Scholar 

  24. Makowski L et al (2001) Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat Med 7(6):699–705

    PubMed  CAS  Google Scholar 

  25. Civelek M et al (2011) Coronary artery endothelial transcriptome in vivo: identification of endoplasmic reticulum stress and enhanced reactive oxygen species by gene connectivity network analysis. Circ Cardiovasc Genet 4(3):243–252

    PubMed  Google Scholar 

  26. Civelek M et al (2009) Chronic endoplasmic reticulum stress activates unfolded protein response in arterial endothelium in regions of susceptibility to atherosclerosis. Circ Res 105(5):453–461

    PubMed  CAS  Google Scholar 

  27. Zeng L et al (2009) Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow. Proc Natl Acad Sci U S A 106(20):8326–8331

    PubMed  CAS  Google Scholar 

  28. Cesari M et al (2005) Is homocysteine important as risk factor for coronary heart disease? Nutr Metab Cardiovasc Dis 15(2):140–147

    PubMed  Google Scholar 

  29. Eikelboom JW et al (1999) Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med 131(5):363–375

    PubMed  CAS  Google Scholar 

  30. Zhou J, Austin RC (2009) Contributions of hyperhomocysteinemia to atherosclerosis: causal relationship and potential mechanisms. Biofactors 35(2):120–129

    PubMed  CAS  Google Scholar 

  31. Zhou J et al (2004) Association of multiple cellular stress pathways with accelerated atherosclerosis in hyperhomocysteinemic apolipoprotein E-deficient mice. Circulation 110(2):207–213

    PubMed  CAS  Google Scholar 

  32. Zhou J et al (2008) Hyperhomocysteinemia induced by methionine supplementation does not independently cause atherosclerosis in C57BL/6J mice. FASEB J 22(7):2569–2578

    PubMed  CAS  Google Scholar 

  33. Zulli A et al (2009) High dietary taurine reduces apoptosis and atherosclerosis in the left main coronary artery: association with reduced CCAAT/enhancer binding protein homologous protein and total plasma homocysteine but not lipidemia. Hypertension 53(6):1017–1022

    PubMed  CAS  Google Scholar 

  34. Tabas I, Ron D (2011) Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 13(3):184–190

    PubMed  CAS  Google Scholar 

  35. Dickhout JG et al (2010) Induction of the unfolded protein response after monocyte to macrophage differentiation augments cell survival in early atherosclerotic lesions. FASEB J 25(2):576–589

    PubMed  Google Scholar 

  36. Tsukano H et al (2010) 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(10):1925–1932

    PubMed  CAS  Google Scholar 

  37. Gao J et al (2011) Involvement of endoplasmic stress protein C/EBP homologous protein in arteriosclerosis acceleration with augmented biological stress responses. Circulation 124(7):830–9

    PubMed  Google Scholar 

  38. Feng B et al (2003) The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 5(9):781–92

    PubMed  CAS  Google Scholar 

  39. Sun Y et al (2009) Free cholesterol accumulation in macrophage membranes activates Toll-like receptors and p38 mitogen-activated protein kinase and induces cathepsin K. Circ Res 104(4):455–465

    PubMed  CAS  Google Scholar 

  40. Li G et al (2009) Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J Cell Biol 186(6):783–792

    PubMed  CAS  Google Scholar 

  41. Timmins JM et al (2009) Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. J Clin Invest 119(10):2925–2941

    PubMed  CAS  Google Scholar 

  42. Seimon TA et al (2010) Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell Metab 12(5):467–482

    PubMed  CAS  Google Scholar 

  43. McCullough KD et al (2001) Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol 21(4):1249–1259

    PubMed  CAS  Google Scholar 

  44. Halterman MW et al (2008) Loss of c/EBP-beta activity promotes the adaptive to apoptotic switch in hypoxic cortical neurons. Mol Cell Neurosci 38(2):125–137

    PubMed  CAS  Google Scholar 

  45. Chiribau CB et al (2010) Molecular symbiosis of CHOP and C/EBP beta isoform LIP contributes to endoplasmic reticulum stress-induced apoptosis. Mol Cell Biol 30(14):3722–3731

    PubMed  CAS  Google Scholar 

  46. Puthalakath H et al (2007) ER stress triggers apoptosis by activating BH3-only protein Bim. Cell 129(7):1337–1349

    PubMed  CAS  Google Scholar 

  47. Ghosh AP et al (2012) CHOP potentially co-operates with FOXO3a in neuronal cells to regulate PUMA and BIM expression in response to ER stress. PLoS One 7(6):e39586

    PubMed  CAS  Google Scholar 

  48. Marciniak SJ et al (2004) CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev 18(24):3066–3077

    PubMed  CAS  Google Scholar 

  49. Seimon TA et al (2009) Macrophage deficiency of p38alpha MAPK promotes apoptosis and plaque necrosis in advanced atherosclerotic lesions in mice. J Clin Invest 119(4):886–898

    PubMed  CAS  Google Scholar 

  50. Seimon TA et al (2006) Combinatorial pattern recognition receptor signaling alters the balance of life and death in macrophages. Proc Natl Acad Sci U S A 103(52):19794–19799

    PubMed  CAS  Google Scholar 

  51. Zhang C et al (2001) Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response. J Biol Chem 276(38):35867–35874

    PubMed  CAS  Google Scholar 

  52. Dong Y et al (2010) Activation of AMP-activated protein kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo. Diabetes 59(6):1386–1396

    PubMed  CAS  Google Scholar 

  53. Pedruzzi E et al (2004) NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells. Mol Cell Biol 24(24):10703–10717

    PubMed  CAS  Google Scholar 

  54. Kedi X et al (2009) Free cholesterol overloading induced smooth muscle cells death and activated both ER- and mitochondrial-dependent death pathway. Atherosclerosis 207(1):123–130

    PubMed  Google Scholar 

  55. Han D et al (2009) IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell 138(3):562–575

    PubMed  CAS  Google Scholar 

  56. Urano F et al (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287(5453):664–666

    PubMed  CAS  Google Scholar 

  57. Lei K, Davis RJ (2003) JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci U S A 100(5):2432–2437

    PubMed  CAS  Google Scholar 

  58. Yamamoto K, Ichijo H, Korsmeyer SJ (1999) BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol 19(12):8469–8478

    PubMed  CAS  Google Scholar 

  59. Upton JP et al (2012) IRE1alpha cleaves select microRNAs during ER stress to derepress translation of proapoptotic caspase-2. Science. doi:10.3410/f.717959717.793462943

    PubMed  Google Scholar 

  60. Bonzon C et al (2006) Caspase-2-induced apoptosis requires bid cleavage: a physiological role for bid in heat shock-induced death. Mol Biol Cell 17(5):2150–2157

    PubMed  CAS  Google Scholar 

  61. Lerner AG et al (2012) IRE1alpha induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab 16(2):250–264

    PubMed  CAS  Google Scholar 

  62. Zhang K, Kaufman RJ (2008) From endoplasmic-reticulum stress to the inflammatory response. Nature 454(7203):455–462

    PubMed  CAS  Google Scholar 

  63. Hotamisligil GS (2010) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140(6):900–917

    PubMed  CAS  Google Scholar 

  64. Li Y et al (2005) Free cholesterol-loaded macrophages are an abundant source of tumor necrosis factor-alpha and interleukin-6: model of NF-kappaB- and map kinase-dependent inflammation in advanced atherosclerosis. J Biol Chem 280(23):21763–21772

    PubMed  CAS  Google Scholar 

  65. Menu P et al (2012) ER stress activates the NLRP3 inflammasome via an UPR-independent pathway. Cell Death Dis 3:e261

    PubMed  CAS  Google Scholar 

  66. Kim JB et al (2011) Paraoxonase-2 modulates stress response of endothelial cells to oxidized phospholipids and a bacterial quorum-sensing molecule. Arterioscler Thromb Vasc Biol 31(11):2624–2633

    PubMed  Google Scholar 

  67. Gargalovic PS et al (2006) Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids. Proc Natl Acad Sci U S A 103(34):12741–12746

    PubMed  CAS  Google Scholar 

  68. Gargalovic PS et al (2006) The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler Thromb Vasc Biol 26(11):2490–2496

    PubMed  CAS  Google Scholar 

  69. Porcheray F et al (2005) Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol 142(3):481–489

    PubMed  CAS  Google Scholar 

  70. Fleming BD, Mosser DM (2011) Regulatory macrophages: setting the threshold for therapy. Eur J Immunol 41(9):2498–2502

    PubMed  CAS  Google Scholar 

  71. Khallou-Laschet J et al (2010) Macrophage plasticity in experimental atherosclerosis. PLoS One 5(1):e8852

    PubMed  Google Scholar 

  72. Oh J et al (2012) Endoplasmic reticulum stress controls M2 macrophage differentiation and foam cell formation. J Biol Chem 287(15):11629–116241

    PubMed  CAS  Google Scholar 

  73. Isa SA et al (2011) M2 macrophages exhibit higher sensitivity to oxLDL-induced lipotoxicity than other monocyte/macrophage subtypes. Lipids Health Dis 10:229

    PubMed  CAS  Google Scholar 

  74. Engin F, Hotamisligil GS (2010) Restoring endoplasmic reticulum function by chemical chaperones: an emerging therapeutic approach for metabolic diseases. Diabetes Obes Metab 12(Suppl 2):108–115

    PubMed  CAS  Google Scholar 

  75. Ozcan U et al (2006) Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313(5790):1137–1140

    PubMed  Google Scholar 

  76. Lenin R et al (2012) Amelioration of glucolipotoxicity-induced endoplasmic reticulum stress by a “chemical chaperone” in human THP-1 monocytes. Exp Diabetes Res 2012:356487

    PubMed  Google Scholar 

  77. Dong Y et al (2010) Reduction of AMP-activated protein kinase alpha2 increases endoplasmic reticulum stress and atherosclerosis in vivo. Circulation 121(6):792–803

    PubMed  CAS  Google Scholar 

  78. Credle JJ et al (2005) On the mechanism of sensing unfolded protein in the endoplasmic reticulum. Proc Natl Acad Sci U S A 102(52):18773–18734

    PubMed  CAS  Google Scholar 

  79. Wiseman RL et al (2010) Flavonol activation defines an unanticipated ligand-binding site in the kinase-RNase domain of IRE1. Mol Cell 38(2):291–304

    PubMed  CAS  Google Scholar 

  80. Perez-Vizcaino F, Duarte J (2010) Flavonols and cardiovascular disease. Mol Aspects Med 31(6):478–494

    PubMed  CAS  Google Scholar 

  81. Choi JS et al (2009) Blockade of oxidized LDL-triggered endothelial apoptosis by quercetin and rutin through differential signaling pathways involving JAK2. J Agric Food Chem 57(5):2079–2086

    PubMed  CAS  Google Scholar 

  82. Chow JM et al (2005) Quercetin, but not rutin and quercitrin, prevention of H2O2-induced apoptosis via anti-oxidant activity and heme oxygenase 1 gene expression in macrophages. Biochem Pharmacol 69(12):1839–51

    PubMed  CAS  Google Scholar 

  83. Yao S et al (2012) Quercetin protects macrophages from oxidized low-density lipoprotein-induced apoptosis by inhibiting the endoplasmic reticulum stress-C/EBP homologous protein pathway. Exp Biol Med (Maywood) 237(7):822–831

    CAS  Google Scholar 

  84. Cox JS, Shamu CE, Walter P (1993) Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell 73(6):1197–11206

    PubMed  CAS  Google Scholar 

  85. Mori K et al (1993) A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell 74(4):743–756

    PubMed  CAS  Google Scholar 

  86. Papa FR et al (2003) Bypassing a kinase activity with an ATP-competitive drug. Science 302(5650):1533–1537

    PubMed  CAS  Google Scholar 

  87. Bouchecareilh M et al (2011) Peptides derived from the bifunctional kinase/RNase enzyme IRE1alpha modulate IRE1alpha activity and protect cells from endoplasmic reticulum stress. FASEB J 25(9):3115–3129

    PubMed  CAS  Google Scholar 

  88. Boyce M et al (2005) A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science 307(5711):935–939

    PubMed  CAS  Google Scholar 

  89. Tsaytler P et al (2011) Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science 332(6025):91–94

    PubMed  CAS  Google Scholar 

  90. Novoa I et al (2001) Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J Cell Biol 153(5):1011–1012

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

A.X.Z. is supported by the Swedish Research Council. I.T. is supported by NIH grants. The authors gratefully acknowledge the members of the Tabas laboratory who contributed to the studies described herein. We also thank Dr. Christopher M. Scull for his helpful discussions and valuable comments.

Author information

Authors and Affiliations

  1. Department of Medicine, Columbia University, New York, NY, USA

    Alex X. Zhou & Ira Tabas

Authors
  1. Alex X. Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ira Tabas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alex X. Zhou.

Additional information

This article is a contribution to the special issue on “The unfolded protein response in immune diseases” - Guest Editors: Richard Blumberg and Arthur Kaser

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, A.X., Tabas, I. The UPR in atherosclerosis. Semin Immunopathol 35, 321–332 (2013). https://doi.org/10.1007/s00281-013-0372-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-013-0372-x

Keywords

Search

Navigation