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. 2001;170(2):132–140. doi: 10.1007/BF03168827

The role of apoptotic cell death in cardiovascular disease

R McLaughlin 1, C J Kelly 1,✉, E Kay 2,1, D Bouchier-Hayes 1
PMCID: PMC7102203  PMID: 11491050

Abstract

Background

Programmed cell death, or apoptesis, is a distinct, managed form of cell death. It is fundamentally different from necrosis. It is a genetically controlled, energy-dependent method of cellular deletion without inflammation. In the cardiovascular system, apoptosis occurs as a primary and secondary event in disease pathogenesis. This review addresses our current understanding of the initiation, propagation and significance of apoptosis in the cardiovascular system, as well as assessing therapeutic potentials arising therefrom.

Methods

A Medline search was performed and relevant publications reviewed. Further articles were obtained from the references of these publications.

Results and conclusions

Apoptotic cell death is a key element in the pathogenesis and progression of ischaemia-reperfusion (IR) injury, cardiac failure, myocardial infarction, atherosclerosis, endothelial dysfunction and the clinical syndromes which these situations produce. Our increased understanding of the role of apoptosis in the pathogenesis of cardiovascular disease offers potential to develop new therapeutic strategies.

Keywords: Smooth Muscle Cell, Programme Cell Death, Clin Invest, Apoptotic Cell Death, Irish Journal

Footnotes

This study was funded by a Health Research Board clinical research fellowship and the North-Eastern Health Board.

References

  • 1.Kerr JRF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide ranging implications in tissue cell kinetics. Br J Cancer. 1972;26:239–57. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Cheng W, Li B, Kajstura J, et al. Stretch induced programmed myocytc cell death. J Clin Invest. 1995;96:2247–59. doi: 10.1172/JCI118280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Beltrami CA, Finato R, Rocco M, et al. The cellular basis of dilated cardiomyopathy in humans. J Mol Cell Cardiol. 1995;27:291–305. doi: 10.1016/S0022-2828(08)80028-4. [DOI] [PubMed] [Google Scholar]
  • 4.Olivetti G, Quaini F, Sala R, et al. Acute myocardial infarction in humans is associated with activation of programmed myocyte cell death in the surviving portion of the heart. J Moll Cell Cardiol. 1996;28:2005–16. doi: 10.1006/jmcc.1996.0193. [DOI] [PubMed] [Google Scholar]
  • 5.Wyllie A. Apoptosis: an overview. Br Med Bull. 1997;53:451–65. doi: 10.1093/oxfordjournals.bmb.a011623. [DOI] [PubMed] [Google Scholar]
  • 6.Ballard KJ, Holt SJ. Cytological and cytochemical studies on cell death and digestion in the foetal rat foot: the role of macrophages and hydrolytic enzymes. J Cell Sci. 1968;3:245–62. doi: 10.1242/jcs.3.2.245. [DOI] [PubMed] [Google Scholar]
  • 7.Bursch W, Oberhammer F, Schute-Hermann Cell death by apoptosis and its protective role against disease. TiPS. 1992;13:245–51. doi: 10.1016/0165-6147(92)90077-j. [DOI] [PubMed] [Google Scholar]
  • 8.Lyons SK, Clarke AR. Apoptosis and carcinogenesis. Br Med Bull. 1997;52:554–69. doi: 10.1093/oxfordjournals.bmb.a011630. [DOI] [PubMed] [Google Scholar]
  • 9.Williams G. Programmed cell death: apoptosis and oncogenesis. Cell. 1991;65:1097–8. doi: 10.1016/0092-8674(91)90002-G. [DOI] [PubMed] [Google Scholar]
  • 10.Harmon B, Takano Y, Winterford C, Gobe G. The role of apoptosis in the response of cells and tumours to mild hyperthermia. Int J Radiat Biol. 1991;59:489–501. doi: 10.1080/09553009114550441. [DOI] [PubMed] [Google Scholar]
  • 11.Williams G. Programmed cell death: apoptosis and oncogenesis. Cell. 1991;65:1097–8. doi: 10.1016/0092-8674(91)90002-G. [DOI] [PubMed] [Google Scholar]
  • 12.Barry M, Behnke C, Eastman A. Activation of programmed cell death (apoptosis) by cisplatin, other anti-cancer drugs and hyperthermia. Biochem Pharmacol. 1990;40:2353–62. doi: 10.1016/0006-2952(90)90733-2. [DOI] [PubMed] [Google Scholar]
  • 13.Glutton S. The importance of oxidative stress in apoptosis. Br Med Bull. 1997;53:662–8. doi: 10.1093/oxfordjournals.bmb.a011637. [DOI] [PubMed] [Google Scholar]
  • 14.Gottlieb RA, Burleson K, Kloner R, Babior B, Engler R. Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest. 1994;94:1621–8. doi: 10.1172/JCI117504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Colucci W. Apoptosis in the heart. New Engl J Med. 1996;335:1224–6. doi: 10.1056/NEJM199610173351610. [DOI] [PubMed] [Google Scholar]
  • 16.Olivetti G, Abbi R, Quaini F. Apoptosis and the failing human heart. New Engl J Med. 1996;336:1131–41. doi: 10.1056/NEJM199704173361603. [DOI] [PubMed] [Google Scholar]
  • 17.Olivetti G, Melissari M, Balbi T, et al. Myocyte nuclear and possible cellular hyperplasia contribute to ventricular remodeling in the hypertrophic senescent heart in humans. J Am Coll Cardiol. 1994;24:140–9. doi: 10.1016/0735-1097(94)90554-1. [DOI] [PubMed] [Google Scholar]
  • 18.Kajstura J, Cheng W, Reiss K, et al. Apoptotic and necrotic cell deaths arc independent contributing variables of infarct size in rats. Lab Invest. 1996;74:86–107. [PubMed] [Google Scholar]
  • 19.Bjorkerud S, Bjorkerud B. Apoptosis is abundant in human atherosclerotic lesions especially in inflammatory cells and may contribute to the accumulation of gruel and plaque instability. Am J Pathol. 1996;149:367–79. [PMC free article] [PubMed] [Google Scholar]
  • 20.Isner J, Kearney M, Bortman S, Passeri J. Apoptosis in human atherosclerosis and restenosis. Circulation. 1995;91:2703–11. doi: 10.1161/01.cir.91.11.2703. [DOI] [PubMed] [Google Scholar]
  • 21.Quaini F, Cigola E, Sala R, et al. Apoptosis in the infarcted human heart. BAM. 1996;6:241–9. [Google Scholar]
  • 22.Arends MJ, Mords RG, Wyllie AH. Apoptosis; The role of the endonudease. Am J Pathol. 1990;136:593–608. [PMC free article] [PubMed] [Google Scholar]
  • 23.Krown K, Page MT, Nguyen C, et al. Tumour necrosis factor alpha induced apoptosis in cardiac myocytes. J Clin Invest. 1996;98:2854–65. doi: 10.1172/JCI119114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Ostling O, Johanson JP. Microelectrophoretic study of radiation induced DNA damage in mammalian cells. Biochem Biophys Res Commun. 1984;123:291–8. doi: 10.1016/0006-291X(84)90411-X. [DOI] [PubMed] [Google Scholar]
  • 25.Fairbairn DW, Olive PL, O’Neill KL. The comet assay: a comprehensive review. Mutat Res. 1995;339:37–59. doi: 10.1016/0165-1110(94)00013-3. [DOI] [PubMed] [Google Scholar]
  • 26.Gorczyca W, Gong J, Ardelt B, Traganos F, Darzynkiewicz Z. The cell cycle related differences in susceptibility of HL-60 cells to apoptosis induced by various antitumor agents. Cancer Res. 1993;53(13):3186–92. [PubMed] [Google Scholar]
  • 27.Gold R. Differentiation between cellular apoptosis and necrosis by the combined use of in situ tailing and nick translation techniques. Lab Invest. 1994;71(2):219–25. [PubMed] [Google Scholar]
  • 28.Meisenholder GW, Martin SJ, Green DR, et al. Events in tpoptosis. Acidification is downstream of protease activation and BCL-2 protection. J Biol Chem. 1996;271(27):16260–2. doi: 10.1074/jbc.271.27.16260. [DOI] [PubMed] [Google Scholar]
  • 29.Ytrehus K, Liu Y, Downey JM. Preconditioning protects ischemic rabbit heart by protein kinase C activation. Am J Physiol. 1994;266(3):H1145–52. doi: 10.1152/ajpheart.1994.266.3.H1145. [DOI] [PubMed] [Google Scholar]
  • 30.Gottlieb RA, Gruol DL, Zhu JY, Engler RL. Preconditioning rabbit cardiomyocytes: role of pH, vacuolar proton ATPase, and apoptosis. J Clin Invest. 1996;97(10):2391–8. doi: 10.1172/JCI118683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Diaz C, Schroit AJ. Role of translocases in the generation of phosphatidylserine asymmetry. J Membrane Biol. 1996;151:1–9. doi: 10.1007/s002329900051. [DOI] [PubMed] [Google Scholar]
  • 32.Fadok VA, Savill JS, Haslet C, et al. Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognise and remove apoptotic cells. J Immunol. 1992;149:4029–35. [PubMed] [Google Scholar]
  • 33.Fadok VA, Voeiker DR, Campbell PA, et al. Exposure of phosphatidylserine on the surface of lymphocytes triggers specific recognition and removal by macrophages. J Immunol. 1992;148:2207–16. [PubMed] [Google Scholar]
  • 34.Andree HAM, Reutelingsperger CPM, Hauptinan R, et al. Binding of vascular anticoagulant to planar phospholipid bilayers. J Biol Chem. 1990;265:4923–8. [PubMed] [Google Scholar]
  • 35.Flynn PD, Byrne CD, Baglin TP, Weissberg PL, Bennett MR. Thrombin generation by apoptotic vascular smooth muscle cells. Blood. 1997;89:4278–84. [PubMed] [Google Scholar]
  • 36.Bebbis M. Studies on cell agony and death: an attempt at classification. In: Dercuck AVS, Knight J, editors. Ciba Foundation symposium on cellular injury. London: J&A Churchill; 1964. pp. 287–328. [Google Scholar]
  • 37.Bebbis MC. Death of a cell. New York, NY: Swift motion picture laboratories; 1958. [Google Scholar]
  • 38.Entman ML, Michael L, Rossen RD, et al. Inflammation in the course of early myocardial ischemia. FASEB J. 1991;5:2529–37. doi: 10.1096/fasebj.5.11.1868978. [DOI] [PubMed] [Google Scholar]
  • 39.Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science. 1995;267:1465–1465. doi: 10.1126/science.7878464. [DOI] [PubMed] [Google Scholar]
  • 40.Narula J, Haider N, Virmani R. Apoptosis in myocytes in end stage heart failure. New Engl J Med. 1996;335:1182–9. doi: 10.1056/NEJM199610173351603. [DOI] [PubMed] [Google Scholar]
  • 41.Hengartner MO, Horvitz HR. The ins and outs of programmed cell death duringC. Elegans development. Phil Trans R Soc Land B. 1994;345:243–8. doi: 10.1098/rstb.1994.0100. [DOI] [PubMed] [Google Scholar]
  • 42.Ellis HM, Horvitz VR. Genetic control of programmed cell death in the nematodeC. elegans. Cell. 1986;44:817–29. doi: 10.1016/0092-8674(86)90004-8. [DOI] [PubMed] [Google Scholar]
  • 43.Hengartner MO, Horvitz HR. C. elegans survival gene ced-9 encodes a functional homologue of the mammalian protooncogene bcl-2. Cell. 1994;76:665–76. doi: 10.1016/0092-8674(94)90506-1. [DOI] [PubMed] [Google Scholar]
  • 44.Wright SC, Wei QS, Zhong J, et al. Purification of a 24-kD protease from apoptosis tumour cells that activates DNA fragmentation. J Exp Med. 1994;180:2113–23. doi: 10.1084/jem.180.6.2113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Longthorne VL, Williams GT. Caspase activation is required for commitment to Fas-mediated apoptosis. EMBO J. 1997;16:3805–12. doi: 10.1093/emboj/16.13.3805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Chinnaiyan AM, O’Rourke K, Yu GL, et al. Signal transduction by DR3, a death domain containing receptor related to TNFR1 and CD95. Science. 1996;274:990–2. doi: 10.1126/science.274.5289.990. [DOI] [PubMed] [Google Scholar]
  • 47.Chinnaiyan AM, O’Rourke K, Tewari M, Dixit VM. FADD, a novel death domain containing protein interacts with the death domain of Fas and initiates apoptosis. Cell. 1995;81:505–12. doi: 10.1016/0092-8674(95)90071-3. [DOI] [PubMed] [Google Scholar]
  • 48.Kitson J, Raven T, Jiang YP, et al. A death domain containing receptor that mediates apoptosis. Nature. 1996;384:372–5. doi: 10.1038/384372a0. [DOI] [PubMed] [Google Scholar]
  • 49.Pan G, O’Rourke K, Chinnaiyan AM, et al. The receptor for the cytotoxic ligand TRAIL. Science. 1997;276:111–3. doi: 10.1126/science.276.5309.111. [DOI] [PubMed] [Google Scholar]
  • 50.Enari M, Talanian RV, Wong WW, Nagata S. Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis. Nature. 1996;380:723–6. doi: 10.1038/380723a0. [DOI] [PubMed] [Google Scholar]
  • 51.Brown R. The BCL-2 family of proteins. Br Med Bull. 1997;53(3):466–77. doi: 10.1093/oxfordjournals.bmb.a011624. [DOI] [PubMed] [Google Scholar]
  • 52.Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce C. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984;226:1097–9. doi: 10.1126/science.6093263. [DOI] [PubMed] [Google Scholar]
  • 53.Ellis HM, Horvitz VR. Genetic control of programmed cell death in the nematodeC. elegans. Cell. 1986;44:817–29. doi: 10.1016/0092-8674(86)90004-8. [DOI] [PubMed] [Google Scholar]
  • 54.Walton MI, Whysong D, O’Connor PM. Constitutive expression of human bcl-2 modulates nitrogen mustard and campothecin induced apoptosis. Cancer Res. 1993;53:1853–61. [PubMed] [Google Scholar]
  • 55.Miyashita T, Reed JC. Bcl-2 oncoprotein blocks chemotherapy induced apoptosis in a human leukemic cell line. Blood. 1993;81:151–7. [PubMed] [Google Scholar]
  • 56.Kajstura J, Mansukhani M, Cheng W, et al. Programmed cell death and expression of the proto-oncogene bcl-2 in myocytes during post-natal maturation of the heart. Exp Cell Res. 1995;219:110–21. doi: 10.1006/excr.1995.1211. [DOI] [PubMed] [Google Scholar]
  • 57.Tin X-M, Oltvai ZN, Kosmeyer SJ. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerisation with Bax. Nature. 1994;369:321–3. doi: 10.1038/369321a0. [DOI] [PubMed] [Google Scholar]
  • 58.Liu X, Kim CN, Yang J, Jemmerson R, Wang X. Induction of apoptotic program in cell free extracts: requirements for dATP and cytochrome c. Cell. 1996;86:147–57. doi: 10.1016/S0092-8674(00)80085-9. [DOI] [PubMed] [Google Scholar]
  • 59.Zamzami N, Susin SA, Marchetti P, et al. Mitochondrial control of nuclear apoptosis. J Exp Med. 1996;184:1331–41. doi: 10.1084/jem.184.4.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Chinnaiyan AM, Orth K, O’Rourke K, et al. Molecular ordering of the cell death pathway: Bcl-2 and bcl-xl function upstream of the CED-3 like apoptotic proteases. J Biol Chem. 1996;271(9):4573–6. doi: 10.1074/jbc.271.9.4573. [DOI] [PubMed] [Google Scholar]
  • 61.Armstrong RC, Aja T, Xiang J, et al. Fas induced activation of the cell death related protease CPP32 is inhibited by Bcl-2 and by ICE family proteases. J Biol Chem. 1996;271:16850–5. doi: 10.1074/jbc.271.9.4978. [DOI] [PubMed] [Google Scholar]
  • 62.Susin SA, Zamzami N, Castedo M, et al. Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J Exp Med. 1996;184:1331–41. doi: 10.1084/jem.184.4.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 1997;275:1132–6. doi: 10.1126/science.275.5303.1132. [DOI] [PubMed] [Google Scholar]
  • 64.Hockenbury DM, Oltavai ZN, Yin XM. Bcl-2 functions in an anti-oxidant pathway to prevent apoptosis. Cell. 1993;75:241–51. doi: 10.1016/0092-8674(93)80066-N. [DOI] [PubMed] [Google Scholar]
  • 65.Jacobson MD, Raff MC. Programmed cell death and bcl-2 protection in very low oxygen. Nature. 1995;374:814–6. doi: 10.1038/374814a0. [DOI] [PubMed] [Google Scholar]
  • 66.Shimizu S, Eguchi Y, Kosaka H, et al. Prevention of hypoxia induced cell death by bcl-2 and bcl-XL. Nature. 1995;374:811–3. doi: 10.1038/374811a0. [DOI] [PubMed] [Google Scholar]
  • 67.Boyd JM, Gallo GJ, Elangovan B. Bik, a novel death inducing protein shares a distinct structural motif with bcl-2 family proteins and interacts with viral and cellular survival promoting proteins. Oncogene. 1995;11:1921–8. [PubMed] [Google Scholar]
  • 68.Yang E, Korsmeyer SJ. Molecular thanatopsis: a discourse on the bcl-2 family and cell death. Blood. 1996;88:386–401. [PubMed] [Google Scholar]
  • 69.Reed JC. Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance. Curr Opin Oncol. 1995;7:541–6. doi: 10.1097/00001622-199511000-00012. [DOI] [PubMed] [Google Scholar]
  • 70.Oitavi ZN, Korsmeyer SJ. Checkpoints of dueling dimers foil cell death. Cell. 1994;79:189–92. doi: 10.1016/0092-8674(94)90188-0. [DOI] [PubMed] [Google Scholar]
  • 71.Pearlman H, Maillard L, Krasinski K, Walsh K. Evidence for the rapid onset of apoptosis in medial smooth muscle cells after balloon injury. Circulation. 1997;95:981–7. doi: 10.1161/01.cir.95.4.981. [DOI] [PubMed] [Google Scholar]
  • 72.Clarke AR, Purdie CA, Harrison DJ, et al. Stabilised p53 facilitates ancuploid clonal divergence in colorectal cancer. Nature. 1993;362:849–52. doi: 10.1038/362849a0. [DOI] [PubMed] [Google Scholar]
  • 73.Long X, Boluyt MO, Hipolito M, et al. p53 and the hypoxia induced apoptosis of cultured neonatal rat cardiac myocytes. J Clin Invest. 1997;99:2635–43. doi: 10.1172/JCI119452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.Kirshenbaum LA, Schneider MD. Adenovirus E1A represses cardiac gene transcription and reactivates DNA synthesis in ventricular cardiomyocytes, via alternate pocket protein and p300 binding domains. J Biol Chem. 1995;270:7791–4. doi: 10.1074/jbc.270.14.7791. [DOI] [PubMed] [Google Scholar]
  • 75.Agah R, Kirshenbaum LA, Abdellatif M, et al. Adenoviral delivery of E2F-1 directs cell cycle re-entry and p53 independent apoptosis in post-mitotic adult cardiomyocytes in vitro. J Clin Invest. 1997;100:2722–8. doi: 10.1172/JCI119817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Bialik S, Geenen DL, Sasson IE, et al. Myocyte apoptosis during acute myocardial infarction in the mouse localizes to hypoxic regions but occurs independently of p53. J Clin Invest. 1997;100:1363–72. doi: 10.1172/JCI119656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Kirshenbaum LA, de Moissac D. The bcl-2 gene product prevents programmed cell death of ventricular myocytes. Circulation. 1997;96:1580–5. doi: 10.1161/01.cir.96.5.1580. [DOI] [PubMed] [Google Scholar]
  • 78.Kirshenbaum LA. Regulators of apoptosis in the heart: a matter of life or death. Can J Cardiol. 1998;14:457–60. [PubMed] [Google Scholar]
  • 79.Furchgott RF. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. JAMA. 1996;276(14):1186–8. doi: 10.1001/jama.276.14.1186. [DOI] [PubMed] [Google Scholar]
  • 80.Vane JR, Botting RM. The role of chemical mediators released by the endothelium in the control of the cardiovascular system. Int J Tissue React. 1992;14(2):55–64. [PubMed] [Google Scholar]
  • 81.Balligand J-L, Cannon P. Nitric oxide synthases and cardiac muscle: autocrine and paracrine influences. Arterioscler Thromb Vasc Biol. 1997;17:1864–8. doi: 10.1161/01.atv.17.10.1846. [DOI] [PubMed] [Google Scholar]
  • 82.Yang X, Chowdhury N, Cai B, et al. Induction of myocardial nitric oxide synthase by cardiac allograft rejection. J Clin Invest. 1994;94:714–21. doi: 10.1172/JCI117390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83.Szabolcs M, Michler R, Robert E, et al. Cellular and molecular cardiovascular disease: apoptosis of cardiac myocytes during cardiac allograft rejection: relation to induction of nitric oxide synthtse. Circulation. 1996;94:1665–73. doi: 10.1161/01.cir.94.7.1665. [DOI] [PubMed] [Google Scholar]
  • 84.Pinsky DJ, Cai B, Yang X, et al. The lethal effects of cytokine induced nitric oxide in cardiac myocytes are blocked by nitric oxide synthase antagonism or transforming growth factor beta. J Clin Invest. 1995;95:677–85. doi: 10.1172/JCI117713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.Kawaguchi K, Shin WS, Wang Y, et al. In vivo gene transfection of human endotheial cell nitric oxide synthase in cardiomyocytes causes apoptosis like cell death; Identification using Sendai virus coated particles. Circulation. 1997;95:2441–7. doi: 10.1161/01.cir.95.10.2441. [DOI] [PubMed] [Google Scholar]
  • 86.Shin WS, Hong Y-U, Peng H-B, et al. Nitric oxide attenuates vascular smooth muscle activation by interferon gamma. J Bid Chem. 1996;271:11317–24. doi: 10.1074/jbc.271.19.11317. [DOI] [PubMed] [Google Scholar]
  • 87.Stellar H. Mechanisms and genes of cellular suicide. Science. 1995;267:1445–62. doi: 10.1126/science.7878463. [DOI] [PubMed] [Google Scholar]
  • 88.Lawrence R, Chang L-J, Siebenlist U, Bressier P, Sonenshein GE. Vascular smooth muscle cells express a constitutive NF-kB ike activity. J Biol Chem. 1994;269:28913–8. [PubMed] [Google Scholar]
  • 89.Obata H, Biro S, Arima N, et al. NF-kB is induced in the nuclei of cultured rat aortic smooth muscle cells by stimulation of various growth factors. Biochem Biophys Res Commun. 1996;224:27–32. doi: 10.1006/bbrc.1996.0979. [DOI] [PubMed] [Google Scholar]
  • 90.Beias RE, Lee JS, Sonenshein GE. Expression of an NF-kB like activity is essential for proliferation of cultured bovine vascular smooth muscle cells. J Clin Invest. 1995;96:2521–7. doi: 10.1172/JCI118313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Brand K, Page S, Rogler G, et al. Activated transcription factor nuclear factor-kB is present in the atherosclerotic lesion. J Clin Invest. 1996;97:1715–22. doi: 10.1172/JCI118598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92.Lindner V, Collins T. Expression of NF-kB and Ik-B by aortic endothelium in an arterial injury model. Am J Patbol. 1996;148:427–38. [PMC free article] [PubMed] [Google Scholar]
  • 93.Laster SM, Wood JG, Goodling LR. Tumour necrosis factor can induce both apoptotic and necrotic forms of cell lysis. J Immunol. 1988;141:2629–43. [PubMed] [Google Scholar]
  • 94.Sharov VG, Sabbah HN, Shimoyama H, et al. Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart Mure. Am J Pathol. 1996;148:141–9. [PMC free article] [PubMed] [Google Scholar]
  • 95.Torre-Amione G, Kapadia S, Lee J. Tumour necrosis factor-(and tumour necrosis factor receptor in the failing human heart. Circulation. 1996;93:704–11. doi: 10.1161/01.cir.93.4.704. [DOI] [PubMed] [Google Scholar]
  • 96.Yamada T, Wang WE, Shioi T. Apoptosis in congestive heart failure induced by viral myocarditis in mice. Circulation. 1996;94:1–32. doi: 10.1007/BF02481740. [DOI] [PubMed] [Google Scholar]
  • 97.Takeda K, Yu ZX, Nishiwaka T. Apoptosis and DNA fagmentation in the bulbis cordis of the developing rat heart. J Mol Cell Cardiol. 1996;28:209–15. doi: 10.1006/jmcc.1996.0020. [DOI] [PubMed] [Google Scholar]
  • 98.James TN. Normal and abnormal consequences of apoptosis in the human heart: from post-natal morphogenesis to paroxysmal arrhythmias. Circulation. 1994;90:556–73. [PubMed] [Google Scholar]
  • 99.Cho A, Courtman DW, Langelli BC. Apoptosis in arteries of the neonatal lamb. Circ Res. 1995;76:168–75. doi: 10.1161/01.res.76.2.168. [DOI] [PubMed] [Google Scholar]
  • 100.Cliff WJ. The tunica media in aging rats. Exp Md Pathol. 1970;13:172–7. doi: 10.1016/0014-4800(70)90004-3. [DOI] [PubMed] [Google Scholar]
  • 101.Han DKM, Haudenschild CC, Hong MK. Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am J Pathol. 1995;147:267–77. [PMC free article] [PubMed] [Google Scholar]
  • 102.Parks DA, Granger DN. Contributions of ischaemia and reperfusion to mucosal lesion formation. Am J Physiol. 1986;250:749–53. doi: 10.1152/ajpgi.1986.250.6.G749. [DOI] [PubMed] [Google Scholar]
  • 103.Sies H. Introduction. Oxidative stress.Academic Press 1985; 1–7.
  • 104.Kloner RA. Does reperfusion injury exist in humans. J Am Coll Cardiol. 1993;21:537–45. doi: 10.1016/0735-1097(93)90700-b. [DOI] [PubMed] [Google Scholar]
  • 105.Cheng W, Li B, Kajstura J. Stretch induced programmed myocyte cell death. J Clin Invest. 1995;96:2247–59. doi: 10.1172/JCI118280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 106.Barinaga M. Forging a path to cell death. Science. 1996;273:735–7. doi: 10.1126/science.273.5276.735. [DOI] [PubMed] [Google Scholar]
  • 107.Seta Y, Shan K, Bozkurt B. Basic mechanisms in heart failure: the cytokine hypothesis. J Cardiac Failure. 1996;2:243–9. doi: 10.1016/S1071-9164(96)80047-9. [DOI] [PubMed] [Google Scholar]
  • 108.Saraste A, Pulkki K, Kallajoki M, et al. Apoptosis in human myocardial infarction. Circulation. 1997;95:320–3. doi: 10.1161/01.cir.95.2.320. [DOI] [PubMed] [Google Scholar]
  • 109.Hirose K, Longo DL, Oppenheim JJ, Matsushima K. Overexpression of manganese superoxide dismutase promotes the survival of tumour cells exposed to interleukin 1, tumour necrosis factor selected anti-cancer drugs and ionising radiation. FASEB J. 1993;7:361–8. doi: 10.1096/fasebj.7.2.8440412. [DOI] [PubMed] [Google Scholar]
  • 110.Forrest VJ, Kang YH, McClain DE. Oxidative stress induced apoptosis prevented by Trolox. Free Radic Biol Med. 1994;16:675–84. doi: 10.1016/0891-5849(94)90182-1. [DOI] [PubMed] [Google Scholar]
  • 111.Wang GH, Redmond HP, Watson RWG, Bouchier-Hayes D. Cellular mechanisms of endothelial cell death during the systemic inflammatory response syndrome. Surg Forum. 1994;80:110–2. [Google Scholar]
  • 112.Teiger E, Than TV, Richard L. Apoptosis in pressure overload induced heart hypertrophy in the rat. J Clin Invest. 1996;97:2891–7. doi: 10.1172/JCI118747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 113.Hamet P, Richard L, Dam TV, et al. Apoptosis in target organs of hypertension. Hypertension. 1995;26:642–8. doi: 10.1161/01.hyp.26.4.642. [DOI] [PubMed] [Google Scholar]
  • 114.Leri A, Claudio PP, Qiong L. Stretch mediated release of antiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin angiotensin system and decreases the bcl-2 to bax protein ratio in the cell. J Clin Invest. 1998;101:1326–42. doi: 10.1172/JCI316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 115.Kajstura J, Cigola E, Malhotra A, et al. Angiotensin II induces apoptosis of adult ventricular myocytes in vitro. J Moll Cell Cardiol. 1997;29:859–70. doi: 10.1006/jmcc.1996.0333. [DOI] [PubMed] [Google Scholar]
  • 116.Mallat Z, Tedgui A, Fontaliran F, et al. Evidence of apoptosis in arrhythmogenic right ventricular failure. New Engl J Med. 1996;335:1190–6. doi: 10.1056/NEJM199610173351604. [DOI] [PubMed] [Google Scholar]
  • 117.Herskowitz A, Choi S, Ansari AA. Cytokine mRNA expression in post-ischaemic/reperfused myocardium. Am J Pathol. 1995;146:419–28. [PMC free article] [PubMed] [Google Scholar]
  • 118.Ikeda U, Ohkawa F, Seino Y. Serum interfeukin-6 levels become elevated in acute myocardial infarction. J Moll Cell Cardiol. 1993;24:579–84. doi: 10.1016/0022-2828(92)91042-4. [DOI] [PubMed] [Google Scholar]
  • 119.Levine B, Kalman J, Mayer L. Elevated circulating levels of tumour necrosis factor-alpha in severe chronic heart failure. New Engl J Med. 1990;323:236–41. doi: 10.1056/NEJM199007263230405. [DOI] [PubMed] [Google Scholar]
  • 120.Aikawa R, Komuro I, Yamazaki T, et al. Oxidative stress activates extracellular signal-regulated kinases through src and ras in cultured cardiac myocytes of neonatal rats. J Clin Invest. 1997;100:1813–21. doi: 10.1172/JCI119709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 121.Jeroudi MO, Hartley CJ, Bolli R. Myocardial reperfusion injury: role of oxygen radicals and potential therapy with antioxidants. Am J Cardiol. 1994;73:1621–8. doi: 10.1016/0002-9149(94)90257-7. [DOI] [PubMed] [Google Scholar]
  • 122.Geng YJ, Libby P. Evidence for apoptosis in advanced human atheroma; co-localization with interleukin-1-(-converting enzyme. Am J Pathol. 1995;147:251–66. [PMC free article] [PubMed] [Google Scholar]
  • 123.Bennett M, Evan G, Schwartz S. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. Clin Invest. 1995;95:2266–74. doi: 10.1172/JCI117917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 124.Escargueil-Blanc I, Salvayre R, Negre-Salvayre A. Necrosis and apoptosis induced by oxidized low density lipoproteins occurs through two calcium dependant pathways in lymphoblastoid pathways. FASEB J. 1994;8:1075–80. doi: 10.1096/fasebj.8.13.7926374. [DOI] [PubMed] [Google Scholar]
  • 125.Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest. 1991;88:1785–92. doi: 10.1172/JCI115499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 126.Witztum JL. The oxidation hypothesis of atherosclerosis.Lancet 1994; 793–5. [DOI] [PubMed]
  • 127.Dimmeler S, Haendeler J, Nehls M, Zeiher AM. Suppression of apoptosis by nitric oxide via inhibition of interleukin-1beta converting cnzyme(ICE)-like and cysteine protease protein (CPP)-32-like proteases. J Exp Med. 1997;185:601–7. doi: 10.1084/jem.185.4.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 128.Aji W, Ravalli S, Szabolcs M, et al. L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice. Circulation. 1997;95:430–7. doi: 10.1161/01.cir.95.2.430. [DOI] [PubMed] [Google Scholar]
  • 129.Isner JM, Kearney M, Berdan LG, et al. Core pathology lab indinp in 425 patients undergoing directional atherectomy for a primary coronary artery stenosis and relationship to subsequent outcome: the CAVEAT study. J Am Coll Cardiol. 1993;21:380–380. [Google Scholar]
  • 130.Frish S, Ruoslahti E. Integrins and anoikis. Curr Opin Cell Biol. 1997;9:701–6. doi: 10.1016/S0955-0674(97)80124-X. [DOI] [PubMed] [Google Scholar]
  • 131.Frish SM, Francisa H. Disruption of endothelial cell matrix interactions induces apoptosis. J Cell Bid. 1994;124:619–26. doi: 10.1083/jcb.124.4.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 132.Pickering JG, Weir L, Jekanowski J. Proliferative activity in peripheral and coronary atherosclerotic plaque among patients undergoing percutaneous revascularization. J Clin Invest. 1993;91:1469–80. doi: 10.1172/JCI116352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 133.DeMeester SL, Buchman TG, Qiu Y, et al. Heat shock induces IkappaB-alpha and prevents stress-induced endothelial cell apoptosis. Arch Sarg. 1997;132(12):1283–7. doi: 10.1001/archsurg.1997.01430360029005. [DOI] [PubMed] [Google Scholar]
  • 134.Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury, I: smooth muscle growth in the absence of endothelium. Lab Invest. 1983;49:327–33. [PubMed] [Google Scholar]
  • 135.Obata H, Biro S, Arima N, et al. NF-kB is induced in the nuclei of cultured rat aortic smooth muscle cells by stimulation of various growth factors. Biochem Biophys Res Commun. 1996;224:27–32. doi: 10.1006/bbrc.1996.0979. [DOI] [PubMed] [Google Scholar]
  • 136.James TN. Complex causes of fatal myocardial infarction. Circulation. 1997;2(5):1696–700. doi: 10.1161/01.cir.96.5.1696. [DOI] [PubMed] [Google Scholar]
  • 137.Isner JM, Kearney M, Bauters C. Use of human tissue specimens obtained by directional atherectomy to study restenosis. Trends Cardiovasc Med. 1994;4:213–21. doi: 10.1016/1050-1738(94)90037-X. [DOI] [PubMed] [Google Scholar]
  • 138.Kearney M, Pieczek A, Haley L, et al. Histopathology of instent restenosis in patients with peripheral artery disease. Circulation. 1997;95:1998–2002. doi: 10.1161/01.cir.95.8.1998. [DOI] [PubMed] [Google Scholar]
  • 139.Steg PG, Tahlil O, Aubailly N. Reduction of restenosis after angioplasty in an atheromatous rabbit model by suicide gene therapy. Circulation. 1997;96(2):408–11. doi: 10.1161/01.cir.96.2.408. [DOI] [PubMed] [Google Scholar]
  • 140.Jeremias I, Kupatt C, Martin-Villalba A, et al. Involvement of CD95/Apo-1/Fas in cell death after myocardial infarction. Circulation. 2000;102:915–1002. doi: 10.1161/01.cir.102.8.915. [DOI] [PubMed] [Google Scholar]
  • 141.Daemen M, Van’tVeer C, Denecker G. Inhibition of apoptosis induced by ischaemia reperfusion prevents inflammation. J Clin Invest. 1999;104:541–9. doi: 10.1172/JCI6974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 142.Wollert K, Heineke J, Westermann J, et al. The cardiac Fas (APO-1/CD95) receptor/Fas ligand system. Circulation. 2000;101:1172–81. doi: 10.1161/01.cir.101.10.1172. [DOI] [PubMed] [Google Scholar]
  • 143.Kupatt C, Habazettl H, Goedecke A. Tumour necrosis factor-(contributes to ischaemia- and reperfusion induced endothelial dysfunction in isolated hearts. Circ Res. 1999;84:392–400. doi: 10.1161/01.res.84.4.392. [DOI] [PubMed] [Google Scholar]
  • 144.Wkaasugi K, Schimmel P. Two distinct cytokines released from a human aminoacyl-t-RNA synthase. Science. 1999;284:147–50. doi: 10.1126/science.284.5411.147. [DOI] [PubMed] [Google Scholar]
  • 145.Daemen M, Van’tVeer C, Heineman E. Pro and antiinflammatory mechanisms in renal reperfusion in mice: modulation by endogenous tumour necrosis factor alpha and interleukin 10. Transplantation. 1999;67:792–800. doi: 10.1097/00007890-199903270-00003. [DOI] [PubMed] [Google Scholar]

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