Advertisement

Basic Research in Cardiology

, Volume 106, Issue 5, pp 749–760 | Cite as

Necrotic cell death in atherosclerosis

  • Wim MartinetEmail author
  • Dorien M. Schrijvers
  • Guido R. Y. De Meyer
Review

Abstract

Necrosis is a type of cell death characterized by a gain in cell volume, swelling of organelles, rupture of the plasma membrane and subsequent loss of intracellular contents. For a long time, the process has been considered as a merely accidental and uncontrolled form of cell death, but accumulating evidence suggests that it can also occur in a regulated fashion. Morphological studies using transmission electron microscopy indicate that the vast majority of dying cells in advanced human atherosclerotic plaques undergo necrosis. Various stimuli in the plaque including high levels of oxidative stress, depletion of cellular ATP, impaired clearance of apoptotic cells and increased intracellular calcium may cause necrotic death. Although the role of necrosis in atherosclerosis remains ill-defined, a growing body of evidence suggests that necrotic death stimulates atherogenesis through induction of inflammation and enlargement of the necrotic core. In addition, necrosis contributes to plaque instability by releasing tissue factor, matrix degrading proteases and pro-angiogenic compounds. Therapeutic agents against necrosis are limited, but efforts have recently been made to inhibit the necrotic pathway or its pro-inflammatory effects.

Keywords

Cell death Necrosis Apoptosis Necrotic core Atherosclerosis 

Notes

Acknowledgments

This work was supported by the Fund for Scientific Research-Flanders and the University of Antwerp.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Ait-Oufella H, Kinugawa K, Zoll J, Simon T, Boddaert J, Heeneman S, Blanc-Brude O, Barateau V, Potteaux S, Merval R, Esposito B, Teissier E, Daemen MJ, Leseche G, Boulanger C, Tedgui A, Mallat Z (2007) Lactadherin deficiency leads to apoptotic cell accumulation and accelerated atherosclerosis in mice. Circulation 115:2168–2177. doi: 10.1161/CIRCULATIONAHA.106.662080 PubMedGoogle Scholar
  2. 2.
    Ait-Oufella H, Pouresmail V, Simon T, Blanc-Brude O, Kinugawa K, Merval R, Offenstadt G, Leseche G, Cohen PL, Tedgui A, Mallat Z (2008) Defective mer receptor tyrosine kinase signaling in bone marrow cells promotes apoptotic cell accumulation and accelerates atherosclerosis. Arterioscler Thromb Vasc Biol 28:1429–1431. doi: 10.1161/ATVBAHA.108.169078 PubMedGoogle Scholar
  3. 3.
    Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlandsson-Harris H, Janson A, Kokkola R, Zhang M, Yang H, Tracey KJ (2000) High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med 192:565–570. doi: 10.1084/jem.192.4.565 PubMedGoogle Scholar
  4. 4.
    Bao L, Li Y, Deng SX, Landry D, Tabas I (2006) Sitosterol-containing lipoproteins trigger free sterol-induced caspase-independent death in ACAT-competent macrophages. J Biol Chem 281:33635–33649. doi: 10.1074/jbc.M606339200 PubMedGoogle Scholar
  5. 5.
    Benko R, Pacher P, Vaslin A, Kollai M, Szabo C (2004) Restoration of the endothelial function in the aortic rings of apolipoprotein E deficient mice by pharmacological inhibition of the nuclear enzyme poly(ADP-ribose) polymerase. Life Sci 75:1255–1261. doi: 10.1016/j.lfs.2004.04.007 PubMedGoogle Scholar
  6. 6.
    Beohar N, Flaherty JD, Davidson CJ, Maynard RC, Robbins JD, Shah AP, Choi JW, MacDonald LA, Jorgensen JP, Pinto JV, Chandra S, Klaus HM, Wang NC, Harris KR, Decker R, Bonow RO (2004) Antirestenotic effects of a locally delivered caspase inhibitor in a balloon injury model. Circulation 109:108–113. doi: 10.1161/01.CIR.0000105724.30980.CD PubMedGoogle Scholar
  7. 7.
    Boisvert WA, Rose DM, Boullier A, Quehenberger O, Sydlaske A, Johnson KA, Curtiss LK, Terkeltaub R (2006) Leukocyte transglutaminase 2 expression limits atherosclerotic lesion size. Arterioscler Thromb Vasc Biol 26:563–569. doi: 10.1161/01.ATV.0000203503.82693.c1 PubMedGoogle Scholar
  8. 8.
    Boyle JJ, Wilson B, Bicknell R, Harrower S, Weissberg PL, Fan TP (2000) Expression of angiogenic factor thymidine phosphorylase and angiogenesis in human atherosclerosis. J Pathol 192:234–242. doi: 10.1002/1096-9896(2000)9999:9999<:AID-PATH699>3.0.CO;2-9 PubMedGoogle Scholar
  9. 9.
    Christofferson DE, Yuan J (2010) Cyclophilin A release as a biomarker of necrotic cell death. Cell Death Differ 17:1942–1943. doi: 10.1038/cdd.2010.123 PubMedGoogle Scholar
  10. 10.
    Crisby M, Kallin B, Thyberg J, Zhivotovsky B, Orrenius S, Kostulas V, Nilsson J (1997) Cell death in human atherosclerotic plaques involves both oncosis and apoptosis. Atherosclerosis 130:17–27. doi: 10.1016/S0021-9150(96)06037-6 PubMedGoogle Scholar
  11. 11.
    Cuchacovich R, Espinoza LR (2009) Does TNF-alpha blockade play any role in cardiovascular risk among rheumatoid arthritis (RA) patients? Clin Rheumatol 28:1217–1220. doi: 10.1007/s10067-009-1208-x PubMedGoogle Scholar
  12. 12.
    de Almeida CJ, Linden R (2005) Phagocytosis of apoptotic cells: a matter of balance. Cell Mol Life Sci 62:1532–1546. doi: 10.1007/s00018-005-4511-y PubMedGoogle Scholar
  13. 13.
    Declercq W, Vanden Berghe T, Vandenabeele P (2009) RIP kinases at the crossroads of cell death and survival. Cell 138:229–232. doi: 10.1016/j.cell.2009.07.006 PubMedGoogle Scholar
  14. 14.
    Degryse B, Bonaldi T, Scaffidi P, Muller S, Resnati M, Sanvito F, Arrigoni G, Bianchi ME (2001) The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells. J Cell Biol 152:1197–1206. doi: 10.1083/jcb.152.6.1197 PubMedGoogle Scholar
  15. 15.
    Degterev A, Hitomi J, Germscheid M, Ch’en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4:313–321. doi: 10.1038/nchembio.83 PubMedGoogle Scholar
  16. 16.
    Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, Cuny GD, Mitchison TJ, Moskowitz MA, Yuan J (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 1:112–119. doi: 10.1038/nchembio711 PubMedGoogle Scholar
  17. 17.
    Di Micco P, Ferrazzi P, Libre L, Mendolicchio L, Quaglia I, De Marco M, Colombo A, Bacci M, Rota LL, Lodigiani C (2009) Intima-media thickness evolution after treatment with infliximab in patients with rheumatoid arthritis. Int J Gen Med 2:141–144. doi: 10.2147/IJGM.S5178 PubMedGoogle Scholar
  18. 18.
    Doran JP, Howie AJ, Townend JN, Bonser RS (1996) Detection of myocardial infarction by immunohistological staining for C9 on formalin fixed, paraffin wax embedded sections. J Clin Pathol 49:34–37. doi: 10.1136/jcp.49.1.34 PubMedGoogle Scholar
  19. 19.
    Erbel C, Dengler TJ, Wangler S, Lasitschka F, Bea F, Wambsganss N, Hakimi M, Bockler D, Katus HA, Gleissner CA (2011) Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability. Basic Res Cardiol 106:125–134. doi: 10.1007/s00395-010-0135-y PubMedGoogle Scholar
  20. 20.
    Erdmann E, Charbonnel B, Wilcox R (2009) Thiazolidinediones and cardiovascular risk—a question of balance. Curr Cardiol Rev 5:155–165. doi: 10.2174/157340309788970333 PubMedGoogle Scholar
  21. 21.
    Fernandez-Ortiz A, Badimon JJ, Falk E, Fuster V, Meyer B, Mailhac A, Weng D, Shah PK, Badimon L (1994) Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol 23:1562–1569. doi: 10.1016/0735-1097(94)90657-2 PubMedGoogle Scholar
  22. 22.
    Festjens N, Vanden Berghe T, Cornelis S, Vandenabeele P (2007) RIP1, a kinase on the crossroads of a cell’s decision to live or die. Cell Death Differ 14:400–410PubMedGoogle Scholar
  23. 23.
    Festjens N, Vanden Berghe T, Vandenabeele P (2006) Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta 1757:1371–1387. doi: 10.1016/j.bbabio.2006.06.014 PubMedGoogle Scholar
  24. 24.
    Fiuza C, Bustin M, Talwar S, Tropea M, Gerstenberger E, Shelhamer JH, Suffredini AF (2003) Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells. Blood 101:2652–2660. doi: 10.1182/blood-2002-05-1300 PubMedGoogle Scholar
  25. 25.
    Freudenberger T, Oppermann M, Heim HK, Mayer P, Kojda G, Schror K, Fischer JW (2010) Proatherogenic effects of estradiol in a model of accelerated atherosclerosis in ovariectomized ApoE-deficient mice. Basic Res Cardiol 105:479–486. doi: 10.1007/s00395-010-0091-6 PubMedGoogle Scholar
  26. 26.
    Godson C, Mitchell S, Harvey K, Petasis NA, Hogg N, Brady HR (2000) Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J Immunol 164:1663–1667PubMedGoogle Scholar
  27. 27.
    Gossl M, Herrmann J, Tang H, Versari D, Galili O, Mannheim D, Rajkumar SV, Lerman LO, Lerman A (2009) Prevention of vasa vasorum neovascularization attenuates early neointima formation in experimental hypercholesterolemia. Basic Res Cardiol 104:695–706. doi: 10.1007/s00395-009-0036-0 PubMedGoogle Scholar
  28. 28.
    Guyton JR, Klemp KF (1996) Development of the lipid-rich core in human atherosclerosis. Arterioscler Thromb Vasc Biol 16:4–11PubMedGoogle Scholar
  29. 29.
    Hans CP, Feng Y, Naura AS, Zerfaoui M, Rezk BM, Xia H, Kaye AD, Matrougui K, Lazartigues E, Boulares AH (2009) Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress. PLoS One 4:e7430. doi: 10.1371/journal.pone.0007430 PubMedGoogle Scholar
  30. 30.
    Hans CP, Zerfaoui M, Naura AS, Catling A, Boulares AH (2008) Differential effects of PARP inhibition on vascular cell survival and ACAT-1 expression favouring atherosclerotic plaque stability. Cardiovasc Res 78:429–439. doi: 10.1093/cvr/cvn018 PubMedGoogle Scholar
  31. 31.
    Hodge S, Hodge G, Brozyna S, Jersmann H, Holmes M, Reynolds PN (2006) Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages. Eur Respir J 28:486–495. doi: 10.1183/09031936.06.00001506 PubMedGoogle Scholar
  32. 32.
    Inoue K, Kawahara K, Biswas KK, Ando K, Mitsudo K, Nobuyoshi M, Maruyama I (2007) HMGB1 expression by activated vascular smooth muscle cells in advanced human atherosclerosis plaques. Cardiovasc Pathol 16:136–143. doi: 10.1016/j.carpath.2006.11.006 PubMedGoogle Scholar
  33. 33.
    Jacobsson LT, Turesson C, Gulfe A, Kapetanovic MC, Petersson IF, Saxne T, Geborek P (2005) Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol 32:1213–1218PubMedGoogle Scholar
  34. 34.
    Jialal I, Devaraj S (2003) Antioxidants and atherosclerosis: don’t throw out the baby with the bath water. Circulation 107:926–928. doi: 10.1161/01.CIR.0000048966.26216.4C PubMedGoogle Scholar
  35. 35.
    Jin ZG, Lungu AO, Xie L, Wang M, Wong C, Berk BC (2004) Cyclophilin A is a proinflammatory cytokine that activates endothelial cells. Arterioscler Thromb Vasc Biol 24:1186–1191. doi: 10.1161/01.ATV.0000130664.51010.28 PubMedGoogle Scholar
  36. 36.
    Kalinina N, Agrotis A, Antropova Y, DiVitto G, Kanellakis P, Kostolias G, Ilyinskaya O, Tararak E, Bobik A (2004) Increased expression of the DNA-binding cytokine HMGB1 in human atherosclerotic lesions: role of activated macrophages and cytokines. Arterioscler Thromb Vasc Biol 24:2320–2325. doi: 10.1161/01.ATV.0000145573.36113.8a PubMedGoogle Scholar
  37. 37.
    Kanellakis P, Agrotis A, Kyaw TS, Koulis C, Ahrens I, Mori S, Takahashi HK, Liu K, Peter K, Nishibori M, Bobik A (2011) High-mobility group box protein 1 neutralization reduces development of diet-induced atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 31:313–319. doi: 10.1161/ATVBAHA.110.218669 PubMedGoogle Scholar
  38. 38.
    Katsuda S, Kaji T (2003) Atherosclerosis and extracellular matrix. J Atheroscler Thromb 10:267–274PubMedGoogle Scholar
  39. 39.
    Kim SH, Lessner SM, Sakurai Y, Galis ZS (2004) Cyclophilin A as a novel biphasic mediator of endothelial activation and dysfunction. Am J Pathol 164:1567–1574. doi: 10.1016/S0002-9440(10)63715-7 PubMedGoogle Scholar
  40. 40.
    Kleinbongard P, Heusch G, Schulz R (2010) TNFalpha in atherosclerosis, myocardial ischemia/reperfusion and heart failure. Pharmacol Ther 127:295–314. doi: 10.1016/j.pharmthera.2010.05.002 PubMedGoogle Scholar
  41. 41.
    Kockx M, Jessup W, Kritharides L (2010) Cyclosporin A and atherosclerosis—cellular pathways in atherogenesis. Pharmacol Ther 128:106–118. doi: 10.1016/j.pharmthera.2010.06.001 PubMedGoogle Scholar
  42. 42.
    Kockx MM, Herman AG (2000) Apoptosis in atherosclerosis: beneficial or detrimental? Cardiovasc Res 45:736–746. doi: 10.1016/S0008-6363(99)00235-7 PubMedGoogle Scholar
  43. 43.
    Konstandin MH, Aksoy H, Wabnitz GH, Volz C, Erbel C, Kirchgessner H, Giannitsis E, Katus HA, Samstag Y, Dengler TJ (2009) Beta2-integrin activation on T cell subsets is an independent prognostic factor in unstable angina pectoris. Basic Res Cardiol 104:341–351. doi: 10.1007/s00395-008-0770-8 PubMedGoogle Scholar
  44. 44.
    Krysko DV, Denecker G, Festjens N, Gabriels S, Parthoens E, D’Herde K, Vandenabeele P (2006) Macrophages use different internalization mechanisms to clear apoptotic and necrotic cells. Cell Death Differ 13:2011–2022. doi: 10.1038/sj.cdd.4401900 PubMedGoogle Scholar
  45. 45.
    Kunishima A, Takemura G, Takatsu H, Hayakawa Y, Kanoh M, Qiu X, Fujiwara T, Fujiwara H (1999) Mode and role of cell death during progression of atherosclerotic lesions in hypercholesterolemic rabbits. Heart Vessels 14:295–306PubMedGoogle Scholar
  46. 46.
    Li S, Sun Y, Liang CP, Thorp EB, Han S, Jehle AW, Saraswathi V, Pridgen B, Kanter JE, Li R, Welch CL, Hasty AH, Bornfeldt KE, Breslow JL, Tabas I, Tall AR (2009) Defective phagocytosis of apoptotic cells by macrophages in atherosclerotic lesions of ob/ob mice and reversal by a fish oil diet. Circ Res 105:1072–1082. doi: 10.1161/CIRCRESAHA.109.199570 PubMedGoogle Scholar
  47. 47.
    Li W, Hellsten A, Jacobsson LS, Blomqvist HM, Olsson AG, Yuan XM (2004) Alpha-tocopherol and astaxanthin decrease macrophage infiltration, apoptosis and vulnerability in atheroma of hyperlipidaemic rabbits. J Mol Cell Cardiol 37:969–978. doi: 10.1016/j.yjmcc.2004.07.009 PubMedGoogle Scholar
  48. 48.
    Lundberg B (1985) Chemical composition and physical state of lipid deposits in atherosclerosis. Atherosclerosis 56:93–110. doi: 10.1016/0021-9150(85)90087-5 PubMedGoogle Scholar
  49. 49.
    Lusis AJ (2000) Atherosclerosis. Nature 407:233–241. doi: 10.1038/35025203 PubMedGoogle Scholar
  50. 50.
    Madamanchi NR, Vendrov A, Runge MS (2005) Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 25:29–38. doi: 10.1161/01.ATV.0000150649.39934.13 PubMedGoogle Scholar
  51. 51.
    Maderna P, Godson C (2003) Phagocytosis of apoptotic cells and the resolution of inflammation. Biochim Biophys Acta 1639:141–151. doi: 10.1016/j.bbadis.2003.09.004 PubMedGoogle Scholar
  52. 52.
    Malesevic M, Kuhling J, Erdmann F, Balsley MA, Bukrinsky MI, Constant SL, Fischer G (2010) A cyclosporin derivative discriminates between extracellular and intracellular cyclophilins. Angew Chem Int Ed Engl 49:213–215. doi: 10.1002/anie.200904529 PubMedGoogle Scholar
  53. 53.
    Mallat Z, Hugel B, Ohan J, Leseche G, Freyssinet JM, Tedgui A (1999) Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation 99:348–353PubMedGoogle Scholar
  54. 54.
    Martinet W, Knaapen MWM, De Meyer GRY, Herman AG, Kockx MM (2002) Elevated levels of oxidative DNA damage and DNA repair enzymes in human atherosclerotic plaques. Circulation 106:927–932. doi: 10.1161/01.CIR.0000026393.47805.21 PubMedGoogle Scholar
  55. 55.
    Meilhac O, Escargueil-Blanc I, Thiers JC, Salvayre R, Negre-Salvayre A (1999) Bcl-2 alters the balance between apoptosis and necrosis, but does not prevent cell death induced by oxidized low density lipoproteins. FASEB J 13:485–494PubMedGoogle Scholar
  56. 56.
    Morimoto K, Janssen WJ, Fessler MB, McPhillips KA, Borges VM, Bowler RP, Xiao YQ, Kench JA, Henson PM, Vandivier RW (2006) Lovastatin enhances clearance of apoptotic cells (efferocytosis) with implications for chronic obstructive pulmonary disease. J Immunol 176:7657–7665PubMedGoogle Scholar
  57. 57.
    Murdaca G, Colombo BM, Puppo F (2009) Anti-TNF-alpha inhibitors: a new therapeutic approach for inflammatory immune-mediated diseases: an update upon efficacy and adverse events. Int J Immunopathol Pharmacol 22:557–565PubMedGoogle Scholar
  58. 58.
    Nagy N, Melchior-Becker A, Fischer JW (2010) Long-term treatment with the AT1-receptor antagonist telmisartan inhibits biglycan accumulation in murine atherosclerosis. Basic Res Cardiol 105:29–38. doi: 10.1007/s00395-009-0051-1 PubMedGoogle Scholar
  59. 59.
    Nazzal D, Cantero AV, Therville N, Segui B, Negre-Salvayre A, Thomsen M, Benoist H (2006) Chlamydia pneumoniae alters mildly oxidized low-density lipoprotein-induced cell death in human endothelial cells, leading to necrosis rather than apoptosis. J Infect Dis 193:136–145. doi: 10.1086/498617 PubMedGoogle Scholar
  60. 60.
    Nigro P, Satoh K, O’Dell MR, Soe NN, Cui Z, Mohan A, Abe J, Alexis JD, Sparks JD, Berk BC (2011) Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient mice. J Exp Med 208:53–66. doi: 10.1084/jem.20101174 PubMedGoogle Scholar
  61. 61.
    Oumouna-Benachour K, Hans CP, Suzuki Y, Naura A, Datta R, Belmadani S, Fallon K, Woods C, Boulares AH (2007) Poly(ADP-ribose) polymerase inhibition reduces atherosclerotic plaque size and promotes factors of plaque stability in apolipoprotein E-deficient mice: effects on macrophage recruitment, nuclear factor-kappaB nuclear translocation, and foam cell death. Circulation 115:2442–2450. doi: 10.1161/CIRCULATIONAHA.106.668756 PubMedGoogle Scholar
  62. 62.
    Pacher P, Szabo C (2007) Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors. Cardiovasc Drug Rev 25:235–260. doi: 10.1111/j.1527-3466.2007.00018.x PubMedGoogle Scholar
  63. 63.
    Peng TI, Jou MJ (2010) Oxidative stress caused by mitochondrial calcium overload. Ann N Y Acad Sci 1201:183–188. doi: 10.1111/j.1749-6632.2010.05634.x PubMedGoogle Scholar
  64. 64.
    Phair RD (1988) Cellular calcium and atherosclerosis: a brief review. Cell Calcium 9:275–284. doi: 10.1016/0143-4160(88)90008-5 PubMedGoogle Scholar
  65. 65.
    Popa C, van Tits LJ, Barrera P, Lemmers HL, van den Hoogen FH, van Riel PL, Radstake TR, Netea MG, Roest M, Stalenhoef AF (2009) Anti-inflammatory therapy with tumour necrosis factor alpha inhibitors improves high-density lipoprotein cholesterol antioxidative capacity in rheumatoid arthritis patients. Ann Rheum Dis 68:868–872. doi: 10.1136/ard.2008.092171 PubMedGoogle Scholar
  66. 66.
    Porto A, Palumbo R, Pieroni M, Aprigliano G, Chiesa R, Sanvito F, Maseri A, Bianchi ME (2006) Smooth muscle cells in human atherosclerotic plaques secrete and proliferate in response to high mobility group box 1 protein. FASEB J 20:2565–2566. doi: 10.1096/fj.06-5867fje PubMedGoogle Scholar
  67. 67.
    Postlethwaite AE, Kang AH (1976) Collagen-and collagen peptide-induced chemotaxis of human blood monocytes. J Exp Med 143:1299–1307PubMedGoogle Scholar
  68. 68.
    Rock KL, Kono H (2008) The inflammatory response to cell death. Annu Rev Pathol 3:99–126. doi: 10.1146/annurev.pathmechdis.3.121806.151456 PubMedGoogle Scholar
  69. 69.
    Rouhiainen A, Tumova S, Valmu L, Kalkkinen N, Rauvala H (2007) Pivotal advance: analysis of proinflammatory activity of highly purified eukaryotic recombinant HMGB1 (amphoterin). J Leukoc Biol 81:49–58. doi: 10.1189/jlb.0306200 PubMedGoogle Scholar
  70. 70.
    Saelens X, Festjens N, Parthoens E, Vanoverberghe I, Kalai M, van Kuppeveld F, Vandenabeele P (2005) Protein synthesis persists during necrotic cell death. J Cell Biol 168:545–551. doi: 10.1083/jcb.200407162 PubMedGoogle Scholar
  71. 71.
    Sarai M, Hartung D, Petrov A, Zhou J, Narula N, Hofstra L, Kolodgie F, Isobe S, Fujimoto S, Vanderheyden JL, Virmani R, Reutelingsperger C, Wong ND, Gupta S, Narula J (2007) Broad and specific caspase inhibitor-induced acute repression of apoptosis in atherosclerotic lesions evaluated by radiolabeled annexin A5 imaging. J Am Coll Cardiol 50:2305–2312. doi: 10.1016/j.jacc.2007.08.044 PubMedGoogle Scholar
  72. 72.
    Satoh K, Matoba T, Suzuki J, O’Dell MR, Nigro P, Cui Z, Mohan A, Pan S, Li L, Jin ZG, Yan C, Abe J, Berk BC (2008) Cyclophilin A mediates vascular remodeling by promoting inflammation and vascular smooth muscle cell proliferation. Circulation 117:3088–3098. doi: 10.1161/CIRCULATIONAHA.107.756106 PubMedGoogle Scholar
  73. 73.
    Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195. doi: 10.1038/nature00858 PubMedGoogle Scholar
  74. 74.
    Scheibner KA, Lutz MA, Boodoo S, Fenton MJ, Powell JD, Horton MR (2006) Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J Immunol 177:1272–1281PubMedGoogle Scholar
  75. 75.
    Schrijvers DM, De Meyer GRY, Kockx MM, Herman AG, Martinet W (2005) Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis. Arterioscler Thromb Vasc Biol 25:1256–1261. doi: 10.1161/01.ATV.0000166517.18801.a7 PubMedGoogle Scholar
  76. 76.
    Seeger FH, Sedding D, Langheinrich AC, Haendeler J, Zeiher AM, Dimmeler S (2010) Inhibition of the p38 MAP kinase in vivo improves number and functional activity of vasculogenic cells and reduces atherosclerotic disease progression. Basic Res Cardiol 105:389–397. doi: 10.1007/s00395-009-0072-9 PubMedGoogle Scholar
  77. 77.
    Seimon TA, Wang Y, Han S, Senokuchi T, Schrijvers DM, Kuriakose G, Tall AR, Tabas IA (2009) Macrophage deficiency of p38alpha MAPK promotes apoptosis and plaque necrosis in advanced atherosclerotic lesions in mice. J Clin Invest 119:886–898. doi: 10.1172/JCI37262 PubMedGoogle Scholar
  78. 78.
    Senior RM, Griffin GL, Mecham RP (1980) Chemotactic activity of elastin-derived peptides. J Clin Invest 66:859–862. doi: 10.1172/JCI109926 PubMedGoogle Scholar
  79. 79.
    Senior RM, Griffin GL, Mecham RP, Wrenn DS, Prasad KU, Urry DW (1984) Val-Gly-Val-Ala-Pro-Gly, a repeating peptide in elastin, is chemotactic for fibroblasts and monocytes. J Cell Biol 99:870–874. doi: 10.1083/jcb.99.3.870 PubMedGoogle Scholar
  80. 80.
    Sherry B, Yarlett N, Strupp A, Cerami A (1992) Identification of cyclophilin as a proinflammatory secretory product of lipopolysaccharide-activated macrophages. Proc Natl Acad Sci USA 89:3511–3515. doi: 10.1073/pnas.89.8.3511 PubMedGoogle Scholar
  81. 81.
    Sun C, Liang C, Ren Y, Zhen Y, He Z, Wang H, Tan H, Pan X, Wu Z (2009) Advanced glycation end products depress function of endothelial progenitor cells via p38 and ERK 1/2 mitogen-activated protein kinase pathways. Basic Res Cardiol 104:42–49. doi: 10.1007/s00395-008-0738-8 PubMedGoogle Scholar
  82. 82.
    Suzuki J, Jin ZG, Meoli DF, Matoba T, Berk BC (2006) Cyclophilin A is secreted by a vesicular pathway in vascular smooth muscle cells. Circ Res 98:811–817. doi: 10.1161/01.RES.0000216405.85080.a6 PubMedGoogle Scholar
  83. 83.
    Szondy Z, Sarang Z, Molnar P, Nemeth T, Piacentini M, Mastroberardino PG, Falasca L, Aeschlimann D, Kovacs J, Kiss I, Szegezdi E, Lakos G, Rajnavolgyi E, Birckbichler PJ, Melino G, Fesus L (2003) Transglutaminase 2−/− mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells. Proc Natl Acad Sci USA 100:7812–7817. doi: 10.1073/pnas.0832466100 PubMedGoogle Scholar
  84. 84.
    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. doi: 10.1161/01.ATV.0000184783.04864.9f PubMedGoogle Scholar
  85. 85.
    Tabas I (2007) Apoptosis and efferocytosis in mouse models of atherosclerosis. Curr Drug Targets 8:1288–1296. doi: 10.2174/138945007783220623 PubMedGoogle Scholar
  86. 86.
    Taylor KR, Trowbridge JM, Rudisill JA, Termeer CC, Simon JC, Gallo RL (2004) Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem 279:17079–17084. doi: 10.1074/jbc.M310859200 PubMedGoogle Scholar
  87. 87.
    Thorp E, Cui D, Schrijvers DM, Kuriakose G, Tabas I (2008) Mertk receptor mutation reduces efferocytosis efficiency and promotes apoptotic cell accumulation and plaque necrosis in atherosclerotic lesions of apoe−/− mice. Arterioscler Thromb Vasc Biol 28:1421–1428. doi: 10.1161/ATVBAHA.108.167197 PubMedGoogle Scholar
  88. 88.
    Thorp E, Kuriakose G, Shah YM, Gonzalez FJ, Tabas I (2007) Pioglitazone increases macrophage apoptosis and plaque necrosis in advanced atherosclerotic lesions of nondiabetic low-density lipoprotein receptor-null mice. Circulation 116:2182–2190. doi: 10.1161/CIRCULATIONAHA.107.698852 PubMedGoogle Scholar
  89. 89.
    Thorp E, Li G, Seimon TA, Kuriakose G, Ron D, Tabas I (2009) Reduced apoptosis and plaque necrosis in advanced atherosclerotic lesions of Apoe−/− and Ldlr−/− mice lacking CHOP. Cell Metab 9:474–481. doi: 10.1016/j.cmet.2009.03.003 PubMedGoogle Scholar
  90. 90.
    Thorp E, Li Y, Bao L, Yao PM, Kuriakose G, Rong J, Fisher EA, Tabas I (2009) Brief report: increased apoptosis in advanced atherosclerotic lesions of Apoe−/− mice lacking macrophage Bcl-2. Arterioscler Thromb Vasc Biol 29:169–172. doi: 10.1161/ATVBAHA.108.176495 PubMedGoogle Scholar
  91. 91.
    Tiyerili V, Zimmer S, Jung S, Wassmann K, Naehle CP, Lutjohann D, Zimmer A, Nickenig G, Wassmann S (2010) CB1 receptor inhibition leads to decreased vascular AT1 receptor expression, inhibition of oxidative stress and improved endothelial function. Basic Res Cardiol 105:465–477. doi: 10.1007/s00395-010-0090-7 PubMedGoogle Scholar
  92. 92.
    Tyurina YY, Serinkan FB, Tyurin VA, Kini V, Yalowich JC, Schroit AJ, Fadeel B, Kagan VE (2004) Lipid antioxidant, etoposide, inhibits phosphatidylserine externalization and macrophage clearance of apoptotic cells by preventing phosphatidylserine oxidation. J Biol Chem 279:6056–6064. doi: 10.1074/jbc.M309929200 PubMedGoogle Scholar
  93. 93.
    Ulloa L, Messmer D (2006) High-mobility group box 1 (HMGB1) protein: friend and foe. Cytokine Growth Factor Rev 17:189–201. doi: 10.1016/j.cytogfr.2006.01.003 PubMedGoogle Scholar
  94. 94.
    Van Herck JL, De Meyer GRY, Martinet W, Bult H, Vrints CJ, Herman AG (2010) Proteasome inhibitor bortezomib promotes a rupture-prone plaque phenotype in ApoE-deficient mice. Basic Res Cardiol 105:39–50. doi: 10.1007/s00395-009-0054-y PubMedGoogle Scholar
  95. 95.
    Van Herck JL, De Meyer GRY, Martinet W, Salgado RA, Shivalkar B, De Mondt R, Van De Ven H, Ludwig A, Van Der Veken P, Van Vaeck L, Bult H, Herman AG, Vrints CJ (2010) Multi-slice computed tomography with N1177 identifies ruptured atherosclerotic plaques in rabbits. Basic Res Cardiol 105:51–59. doi: 10.1007/s00395-009-0052-0 PubMedGoogle Scholar
  96. 96.
    Vanden Berghe T, Kalai M, Denecker G, Meeus A, Saelens X, Vandenabeele P (2006) Necrosis is associated with IL-6 production but apoptosis is not. Cell Signal 18:328–335. doi: 10.1016/j.cellsig.2005.05.003 Google Scholar
  97. 97.
    Vejux A, Lizard G (2009) Cytotoxic effects of oxysterols associated with human diseases: induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis. Mol Aspects Med 30:153–170. doi: 10.1016/j.mam.2009.02.006 PubMedGoogle Scholar
  98. 98.
    Victor VM, Apostolova N, Herance R, Hernandez-Mijares A, Rocha M (2009) Oxidative stress and mitochondrial dysfunction in atherosclerosis: mitochondria-targeted antioxidants as potential therapy. Curr Med Chem 16:4654–4667. doi: 10.2174/092986709789878265 PubMedGoogle Scholar
  99. 99.
    Virmani R, Burke A, Willerson J, Farb A, Narula J, Kolodgie F (2007) The pathology of vulnerable plaque. In: Virmani R, Narula J, Leon M, Willerson J (eds) The vulnerable atherosclerotic plaque: strategies for diagnosis and management. Blackwell Futura, Malden, pp 21–36Google Scholar
  100. 100.
    Wei Y, Heng G, Ben H (2010) Pro-inflammatory activities induced by CyPA-EMMPRIN interaction in monocytes. Atherosclerosis 213:415–421. doi: 10.1016/j.atherosclerosis.2010.09.033 Google Scholar
  101. 101.
    Yang H, Tracey KJ (2010) Targeting HMGB1 in inflammation. Biochim Biophys Acta 1799:149–156. doi: 10.1016/j.bbagrm.2009.11.019 PubMedGoogle Scholar
  102. 102.
    Yang H, Wang H, Czura CJ, Tracey KJ (2005) The cytokine activity of HMGB1. J Leukoc Biol 78:1–8. doi: 10.1189/jlb.1104648 PubMedGoogle Scholar
  103. 103.
    Yang J, Huang C, Yang J, Jiang H, Ding J (2011) Statins attenuate high mobility group box-1 protein induced vascular endothelial activation : a key role for TLR4/NF-kappaB signaling pathway. Mol Cell Biochem 345:189–195. doi: 10.1007/s11010-010-0572-9 Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Wim Martinet
    • 1
    Email author
  • Dorien M. Schrijvers
    • 1
  • Guido R. Y. De Meyer
    • 1
  1. 1.Division of PharmacologyUniversity of AntwerpAntwerpBelgium

Personalised recommendations