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. 2001 Mar;109(Suppl 1):27–34. doi: 10.1289/ehp.01109s127

Molecular and cellular mechanisms of cardiotoxicity.

Y J Kang 1
PMCID: PMC1240540  PMID: 11250803

Abstract

Cardiotoxicity resulting from detrimental environmental insults has been recognized for a long time. However, extensive studies of the mechanisms involved had not been undertaken until recent years. Advances in molecular biology provide powerful tools and make such studies possible. We are gathering information about cellular events, signaling pathways, and molecular mechanisms of myocardial toxicologic responses to environmental toxicants and pollutants. Severe acute toxic insults cause cardiac cell death instantly. In the early response to mild environmental stimuli, biochemical changes such as alterations in calcium homeostasis occur. These may lead to cardiac arrhythmia, which most often is reversible. Prolonged stimuli activate transcription factors such as activator protein-1 through elevation of intracellular calcium and the subsequent activation of calcineurin. Upregulation by activated transcription factors of hypertrophic genes results in heart hypertrophy, which is a short-term adaptive response to detrimental factors. However, further development of hypertrophy will lead to severe and irreversible cardiomyopathy, and eventually heart failure. From cardiac hypertrophy to heart failure, myocardial cells undergo extensive biochemical and molecular changes. Cardiac hypertrophy causes tissue hypoperfusion, which activates compensatory mechanisms such as production of angiotensin II and norepinephrine. Both further stimulate cardiac hypertrophy and, importantly, activate counterregulatory mechanisms including overexpression of atrial natriuretic peptide and b-type natriuretic peptide, and production of cytokines such as tumor necrosis factor-alpha. This counterregulation leads to myocardial remodeling as well as cell death through apoptosis and necrosis. Cell death through activation of mitochondrial factors and other pathways constitutes an important cellular mechanism of heart failure. Our current knowledge of cardiotoxicity is limited. Further extensive studies are warranted for a comprehensive understanding of this field.

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Selected References

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  1. Abas L., Bogoyevitch M. A., Guppy M. Mitochondrial ATP production is necessary for activation of the extracellular-signal-regulated kinases during ischaemia/reperfusion in rat myocyte-derived H9c2 cells. Biochem J. 2000 Jul 1;349(Pt 1):119–126. doi: 10.1042/0264-6021:3490119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adams J. M., Cory S. The Bcl-2 protein family: arbiters of cell survival. Science. 1998 Aug 28;281(5381):1322–1326. doi: 10.1126/science.281.5381.1322. [DOI] [PubMed] [Google Scholar]
  3. Anversa P., Capasso J. M. Cardiac hypertrophy and ventricular remodeling. Lab Invest. 1991 Apr;64(4):441–445. [PubMed] [Google Scholar]
  4. Anversa P., Ricci R., Olivetti G. Quantitative structural analysis of the myocardium during physiologic growth and induced cardiac hypertrophy: a review. J Am Coll Cardiol. 1986 May;7(5):1140–1149. doi: 10.1016/s0735-1097(86)80236-4. [DOI] [PubMed] [Google Scholar]
  5. Balasubramanyam M., Mohan V. Signal transduction during cardiac hypertrophy: new insights. Indian Heart J. 2000 Mar-Apr;52(2):226–232. [PubMed] [Google Scholar]
  6. Bogoyevitch M. A., Gillespie-Brown J., Ketterman A. J., Fuller S. J., Ben-Levy R., Ashworth A., Marshall C. J., Sugden P. H. Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion. Circ Res. 1996 Aug;79(2):162–173. doi: 10.1161/01.res.79.2.162. [DOI] [PubMed] [Google Scholar]
  7. Bogoyevitch M. A., Sugden P. H. The role of protein kinases in adaptational growth of the heart. Int J Biochem Cell Biol. 1996 Jan;28(1):1–12. doi: 10.1016/1357-2725(95)00142-5. [DOI] [PubMed] [Google Scholar]
  8. Brand T., Sharma H. S., Fleischmann K. E., Duncker D. J., McFalls E. O., Verdouw P. D., Schaper W. Proto-oncogene expression in porcine myocardium subjected to ischemia and reperfusion. Circ Res. 1992 Dec;71(6):1351–1360. doi: 10.1161/01.res.71.6.1351. [DOI] [PubMed] [Google Scholar]
  9. Buck E. D., Lachnit W. G., Pessah I. N. Mechanisms of delta-hexachlorocyclohexane toxicity: I. Relationship between altered ventricular myocyte contractility and ryanodine receptor function. J Pharmacol Exp Ther. 1999 Apr;289(1):477–485. [PubMed] [Google Scholar]
  10. Cheng T. H., Shih N. L., Chen S. Y., Wang D. L., Chen J. J. Reactive oxygen species modulate endothelin-I-induced c-fos gene expression in cardiomyocytes. Cardiovasc Res. 1999 Mar;41(3):654–662. doi: 10.1016/s0008-6363(98)00275-2. [DOI] [PubMed] [Google Scholar]
  11. Cheng W., Li B., Kajstura J., Li P., Wolin M. S., Sonnenblick E. H., Hintze T. H., Olivetti G., Anversa P. Stretch-induced programmed myocyte cell death. J Clin Invest. 1995 Nov;96(5):2247–2259. doi: 10.1172/JCI118280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chien K. R., Knowlton K. U., Zhu H., Chien S. Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response. FASEB J. 1991 Dec;5(15):3037–3046. doi: 10.1096/fasebj.5.15.1835945. [DOI] [PubMed] [Google Scholar]
  13. Cook S. A., Sugden P. H., Clerk A. Regulation of bcl-2 family proteins during development and in response to oxidative stress in cardiac myocytes: association with changes in mitochondrial membrane potential. Circ Res. 1999 Nov 12;85(10):940–949. doi: 10.1161/01.res.85.10.940. [DOI] [PubMed] [Google Scholar]
  14. Cuenda A., Rouse J., Doza Y. N., Meier R., Cohen P., Gallagher T. F., Young P. R., Lee J. C. SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett. 1995 May 8;364(2):229–233. doi: 10.1016/0014-5793(95)00357-f. [DOI] [PubMed] [Google Scholar]
  15. Daugas E., Susin S. A., Zamzami N., Ferri K. F., Irinopoulou T., Larochette N., Prévost M. C., Leber B., Andrews D., Penninger J. Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis. FASEB J. 2000 Apr;14(5):729–739. [PubMed] [Google Scholar]
  16. Depre C., Taegtmeyer H. Metabolic aspects of programmed cell survival and cell death in the heart. Cardiovasc Res. 2000 Feb;45(3):538–548. doi: 10.1016/s0008-6363(99)00266-7. [DOI] [PubMed] [Google Scholar]
  17. Diamond M. I., Miner J. N., Yoshinaga S. K., Yamamoto K. R. Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. Science. 1990 Sep 14;249(4974):1266–1272. doi: 10.1126/science.2119054. [DOI] [PubMed] [Google Scholar]
  18. Dorn G. W., 2nd, Brown J. H. Gq signaling in cardiac adaptation and maladaptation. Trends Cardiovasc Med. 1999 Jan-Feb;9(1-2):26–34. doi: 10.1016/s1050-1738(99)00004-3. [DOI] [PubMed] [Google Scholar]
  19. Earm Y. E., Ho W. K., So I. Effects of adriamycin on ionic currents in single cardiac myocytes of the rabbit. J Mol Cell Cardiol. 1994 Feb;26(2):163–172. doi: 10.1006/jmcc.1994.1019. [DOI] [PubMed] [Google Scholar]
  20. Eguchi Y., Shimizu S., Tsujimoto Y. Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res. 1997 May 15;57(10):1835–1840. [PubMed] [Google Scholar]
  21. Eliot R. S., Clayton F. C., Pieper G. M., Todd G. L. Influence of environmental stress on pathogenesis of sudden cardiac death. Fed Proc. 1977 Apr;36(5):1719–1724. [PubMed] [Google Scholar]
  22. Evans T., Reitman M., Felsenfeld G. An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5976–5980. doi: 10.1073/pnas.85.16.5976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ferrari R., Ceconi C., Curello S., Ferrari F., Confortini R., Pepi P., Visioli O. Activation of the neuroendocrine response in heart failure: adaptive or maladaptive process? Cardiovasc Drugs Ther. 1996 Nov;10 (Suppl 2):623–629. doi: 10.1007/BF00052509. [DOI] [PubMed] [Google Scholar]
  24. Ferrari R. The role of TNF in cardiovascular disease. Pharmacol Res. 1999 Aug;40(2):97–105. doi: 10.1006/phrs.1998.0463. [DOI] [PubMed] [Google Scholar]
  25. Francis G. S., Carlyle W. C. Hypothetical pathways of cardiac myocyte hypertrophy: response to myocardial injury. Eur Heart J. 1993 Nov;14 (Suppl J):49–56. [PubMed] [Google Scholar]
  26. Francis G. S., Chu C. Compensatory and maladaptive responses to cardiac dysfunction. Curr Opin Cardiol. 1995 May;10(3):260–267. doi: 10.1097/00001573-199505000-00005. [DOI] [PubMed] [Google Scholar]
  27. Gorza L., Menabó R., Di Lisa F., Vitadello M. Troponin T cross-linking in human apoptotic cardiomyocytes. Am J Pathol. 1997 Jun;150(6):2087–2097. [PMC free article] [PubMed] [Google Scholar]
  28. Gottlieb R. A., Burleson K. O., Kloner R. A., Babior B. M., Engler R. L. Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest. 1994 Oct;94(4):1621–1628. doi: 10.1172/JCI117504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Green D. R., Reed J. C. Mitochondria and apoptosis. Science. 1998 Aug 28;281(5381):1309–1312. doi: 10.1126/science.281.5381.1309. [DOI] [PubMed] [Google Scholar]
  30. He S. Y., Matoba R., Sodesaki K., Fujitani N., Ito Y. Morphological and morphometric investigation of cardiac lesions after chronic administration of methamphetamine in rats. Nihon Hoigaku Zasshi. 1996 Apr;50(2):63–71. [PubMed] [Google Scholar]
  31. Hieble J. P. Adrenoceptor subclassification: an approach to improved cardiovascular therapeutics. Pharm Acta Helv. 2000 Mar;74(2-3):163–171. doi: 10.1016/s0031-6865(99)00030-8. [DOI] [PubMed] [Google Scholar]
  32. Ho A. K., Duffield R. 6-Hydroxydopamine-induced developmental cardiac alterations in morphology, calmodulin content, and K(2+)-mediated [Ca(2+)](i)Transient of chicken cardiomyocytes. J Mol Cell Cardiol. 2000 Jul;32(7):1315–1326. doi: 10.1006/jmcc.2000.1165. [DOI] [PubMed] [Google Scholar]
  33. Ho P. D., Zechner D. K., He H., Dillmann W. H., Glembotski C. C., McDonough P. M. The Raf-MEK-ERK cascade represents a common pathway for alteration of intracellular calcium by Ras and protein kinase C in cardiac myocytes. J Biol Chem. 1998 Aug 21;273(34):21730–21735. doi: 10.1074/jbc.273.34.21730. [DOI] [PubMed] [Google Scholar]
  34. Hoey T., Sun Y. L., Williamson K., Xu X. Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins. Immunity. 1995 May;2(5):461–472. doi: 10.1016/1074-7613(95)90027-6. [DOI] [PubMed] [Google Scholar]
  35. Holtz J. Pathophysiology of heart failure and the renin-angiotensin-system. Basic Res Cardiol. 1993;88 (Suppl 1):183–201. doi: 10.1007/978-3-642-72497-8_13. [DOI] [PubMed] [Google Scholar]
  36. Ito H., Hirata Y., Adachi S., Tanaka M., Tsujino M., Koike A., Nogami A., Murumo F., Hiroe M. Endothelin-1 is an autocrine/paracrine factor in the mechanism of angiotensin II-induced hypertrophy in cultured rat cardiomyocytes. J Clin Invest. 1993 Jul;92(1):398–403. doi: 10.1172/JCI116579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Izumo S., Nadal-Ginard B., Mahdavi V. Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci U S A. 1988 Jan;85(2):339–343. doi: 10.1073/pnas.85.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Jalili T., Takeishi Y., Walsh R. A. Signal transduction during cardiac hypertrophy: the role of G alpha q, PLC beta I, and PKC. Cardiovasc Res. 1999 Oct;44(1):5–9. doi: 10.1016/s0008-6363(99)00211-4. [DOI] [PubMed] [Google Scholar]
  39. James J., Robbins J. Molecular remodeling of cardiac contractile function. Am J Physiol. 1997 Nov;273(5 Pt 2):H2105–H2118. doi: 10.1152/ajpheart.1997.273.5.H2105. [DOI] [PubMed] [Google Scholar]
  40. James T. N. Normal and abnormal consequences of apoptosis in the human heart. From postnatal morphogenesis to paroxysmal arrhythmias. Circulation. 1994 Jul;90(1):556–573. [PubMed] [Google Scholar]
  41. Jiang Y., Chen C., Li Z., Guo W., Gegner J. A., Lin S., Han J. Characterization of the structure and function of a new mitogen-activated protein kinase (p38beta). J Biol Chem. 1996 Jul 26;271(30):17920–17926. doi: 10.1074/jbc.271.30.17920. [DOI] [PubMed] [Google Scholar]
  42. Jones L. G., Rozich J. D., Tsutsui H., Cooper G., 4th Endothelin stimulates multiple responses in isolated adult ventricular cardiac myocytes. Am J Physiol. 1992 Nov;263(5 Pt 2):H1447–H1454. doi: 10.1152/ajpheart.1992.263.5.H1447. [DOI] [PubMed] [Google Scholar]
  43. Jürgensmeier J. M., Xie Z., Deveraux Q., Ellerby L., Bredesen D., Reed J. C. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4997–5002. doi: 10.1073/pnas.95.9.4997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Kajstura J., Cheng W., Reiss K., Clark W. A., Sonnenblick E. H., Krajewski S., Reed J. C., Olivetti G., Anversa P. Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Lab Invest. 1996 Jan;74(1):86–107. [PubMed] [Google Scholar]
  45. Kang P. M., Izumo S. Apoptosis and heart failure: A critical review of the literature. Circ Res. 2000 Jun 9;86(11):1107–1113. doi: 10.1161/01.res.86.11.1107. [DOI] [PubMed] [Google Scholar]
  46. Kang Y. J., Zhou Z. X., Wang G. W., Buridi A., Klein J. B. Suppression by metallothionein of doxorubicin-induced cardiomyocyte apoptosis through inhibition of p38 mitogen-activated protein kinases. J Biol Chem. 2000 May 5;275(18):13690–13698. doi: 10.1074/jbc.275.18.13690. [DOI] [PubMed] [Google Scholar]
  47. Kang Y. J., Zhou Z. X., Wu H., Wang G. W., Saari J. T., Klein J. B. Metallothionein inhibits myocardial apoptosis in copper-deficient mice: role of atrial natriuretic peptide. Lab Invest. 2000 May;80(5):745–757. doi: 10.1038/labinvest.3780078. [DOI] [PubMed] [Google Scholar]
  48. Kariya K., Karns L. R., Simpson P. C. An enhancer core element mediates stimulation of the rat beta-myosin heavy chain promoter by an alpha 1-adrenergic agonist and activated beta-protein kinase C in hypertrophy of cardiac myocytes. J Biol Chem. 1994 Feb 4;269(5):3775–3782. [PubMed] [Google Scholar]
  49. Karns L. R., Kariya K., Simpson P. C. M-CAT, CArG, and Sp1 elements are required for alpha 1-adrenergic induction of the skeletal alpha-actin promoter during cardiac myocyte hypertrophy. Transcriptional enhancer factor-1 and protein kinase C as conserved transducers of the fetal program in cardiac growth. J Biol Chem. 1995 Jan 6;270(1):410–417. doi: 10.1074/jbc.270.1.410. [DOI] [PubMed] [Google Scholar]
  50. Katz A. M. The cardiomyopathy of overload: an unnatural growth response in the hypertrophied heart. Ann Intern Med. 1994 Sep 1;121(5):363–371. doi: 10.7326/0003-4819-121-5-199409010-00009. [DOI] [PubMed] [Google Scholar]
  51. Keizer H. G., Pinedo H. M., Schuurhuis G. J., Joenje H. Doxorubicin (adriamycin): a critical review of free radical-dependent mechanisms of cytotoxicity. Pharmacol Ther. 1990;47(2):219–231. doi: 10.1016/0163-7258(90)90088-j. [DOI] [PubMed] [Google Scholar]
  52. Kelly R. A., Eid H., Krämer B. K., O'Neill M., Liang B. T., Reers M., Smith T. W. Endothelin enhances the contractile responsiveness of adult rat ventricular myocytes to calcium by a pertussis toxin-sensitive pathway. J Clin Invest. 1990 Oct;86(4):1164–1171. doi: 10.1172/JCI114822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Kohno I., Komori S., Yamamoto K., Sano S., Ishihara T., Umetani K., Sawanobori T., Ijiri H., Tamura K. Hypertrophic cardiomyopathy complicated with cardiac amyloidosis. Intern Med. 2000 Aug;39(8):637–640. doi: 10.2169/internalmedicine.39.637. [DOI] [PubMed] [Google Scholar]
  54. Kolbeck-Rühmkorff C., Zimmer H. G. Proto-oncogene expression in the isolated working rat heart: combination of pressure and volume overload with norepinephrine. J Mol Cell Cardiol. 1995 Jan;27(1):501–511. doi: 10.1016/s0022-2828(08)80045-4. [DOI] [PubMed] [Google Scholar]
  55. Komuro I., Yazaki Y. Control of cardiac gene expression by mechanical stress. Annu Rev Physiol. 1993;55:55–75. doi: 10.1146/annurev.ph.55.030193.000415. [DOI] [PubMed] [Google Scholar]
  56. Kovacic-Milivojevic B., Wong V. S., Gardner D. G. Selective regulation of the atrial natriuretic peptide gene by individual components of the activator protein-1 complex. Endocrinology. 1996 Mar;137(3):1108–1117. doi: 10.1210/endo.137.3.8603581. [DOI] [PubMed] [Google Scholar]
  57. Kroemer G., Zamzami N., Susin S. A. Mitochondrial control of apoptosis. Immunol Today. 1997 Jan;18(1):44–51. doi: 10.1016/s0167-5699(97)80014-x. [DOI] [PubMed] [Google Scholar]
  58. Krown K. A., Page M. T., Nguyen C., Zechner D., Gutierrez V., Comstock K. L., Glembotski C. C., Quintana P. J., Sabbadini R. A. Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death. J Clin Invest. 1996 Dec 15;98(12):2854–2865. doi: 10.1172/JCI119114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Lange L. G., Schreiner G. F. Immune mechanisms of cardiac disease. N Engl J Med. 1994 Apr 21;330(16):1129–1135. doi: 10.1056/NEJM199404213301607. [DOI] [PubMed] [Google Scholar]
  60. Lechner C., Zahalka M. A., Giot J. F., Møller N. P., Ullrich A. ERK6, a mitogen-activated protein kinase involved in C2C12 myoblast differentiation. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4355–4359. doi: 10.1073/pnas.93.9.4355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Lee J. C., Laydon J. T., McDonnell P. C., Gallagher T. F., Kumar S., Green D., McNulty D., Blumenthal M. J., Heys J. R., Landvatter S. W. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature. 1994 Dec 22;372(6508):739–746. doi: 10.1038/372739a0. [DOI] [PubMed] [Google Scholar]
  62. Lefrak E. A., Pitha J., Rosenheim S., Gottlieb J. A. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer. 1973 Aug;32(2):302–314. doi: 10.1002/1097-0142(197308)32:2<302::aid-cncr2820320205>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  63. Leist M., Nicotera P. The shape of cell death. Biochem Biophys Res Commun. 1997 Jul 9;236(1):1–9. doi: 10.1006/bbrc.1997.6890. [DOI] [PubMed] [Google Scholar]
  64. Leist M., Single B., Castoldi A. F., Kühnle S., Nicotera P. Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med. 1997 Apr 21;185(8):1481–1486. doi: 10.1084/jem.185.8.1481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Leist M., Single B., Naumann H., Fava E., Simon B., Kühnle S., Nicotera P. Inhibition of mitochondrial ATP generation by nitric oxide switches apoptosis to necrosis. Exp Cell Res. 1999 Jun 15;249(2):396–403. doi: 10.1006/excr.1999.4514. [DOI] [PubMed] [Google Scholar]
  66. Lemasters J. J., Nieminen A. L., Qian T., Trost L. C., Herman B. The mitochondrial permeability transition in toxic, hypoxic and reperfusion injury. Mol Cell Biochem. 1997 Sep;174(1-2):159–165. [PubMed] [Google Scholar]
  67. Lenczowski J. M., Dominguez L., Eder A. M., King L. B., Zacharchuk C. M., Ashwell J. D. Lack of a role for Jun kinase and AP-1 in Fas-induced apoptosis. Mol Cell Biol. 1997 Jan;17(1):170–181. doi: 10.1128/mcb.17.1.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Levin E. R., Gardner D. G., Samson W. K. Natriuretic peptides. N Engl J Med. 1998 Jul 30;339(5):321–328. doi: 10.1056/NEJM199807303390507. [DOI] [PubMed] [Google Scholar]
  69. Li H., Zhu H., Xu C. J., Yuan J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 1998 Aug 21;94(4):491–501. doi: 10.1016/s0092-8674(00)81590-1. [DOI] [PubMed] [Google Scholar]
  70. Li Z., Bing O. H., Long X., Robinson K. G., Lakatta E. G. Increased cardiomyocyte apoptosis during the transition to heart failure in the spontaneously hypertensive rat. Am J Physiol. 1997 May;272(5 Pt 2):H2313–H2319. doi: 10.1152/ajpheart.1997.272.5.H2313. [DOI] [PubMed] [Google Scholar]
  71. Limaye D. A., Shaikh Z. A. Cytotoxicity of cadmium and characteristics of its transport in cardiomyocytes. Toxicol Appl Pharmacol. 1999 Jan 1;154(1):59–66. doi: 10.1006/taap.1998.8575. [DOI] [PubMed] [Google Scholar]
  72. Lin Q., Schwarz J., Bucana C., Olson E. N. Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C. Science. 1997 May 30;276(5317):1404–1407. doi: 10.1126/science.276.5317.1404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Lorell B. H. Transition from hypertrophy to failure. Circulation. 1997 Dec 2;96(11):3824–3827. [PubMed] [Google Scholar]
  74. Maass A., Leinwand L. A. Animal models of hypertrophic cardiomyopathy. Curr Opin Cardiol. 2000 May;15(3):189–196. doi: 10.1097/00001573-200005000-00012. [DOI] [PubMed] [Google Scholar]
  75. Mann D. L., Kent R. L., Cooper G., 4th Load regulation of the properties of adult feline cardiocytes: growth induction by cellular deformation. Circ Res. 1989 Jun;64(6):1079–1090. doi: 10.1161/01.res.64.6.1079. [DOI] [PubMed] [Google Scholar]
  76. Maulik N., Goswami S., Galang N., Das D. K. Differential regulation of Bcl-2, AP-1 and NF-kappaB on cardiomyocyte apoptosis during myocardial ischemic stress adaptation. FEBS Lett. 1999 Jan 29;443(3):331–336. doi: 10.1016/s0014-5793(98)01719-0. [DOI] [PubMed] [Google Scholar]
  77. McCarthy N. J., Evan G. I. Methods for detecting and quantifying apoptosis. Curr Top Dev Biol. 1998;36:259–278. doi: 10.1016/s0070-2153(08)60507-4. [DOI] [PubMed] [Google Scholar]
  78. McKenzie J. C., Kelley K. B., Merisko-Liversidge E. M., Kennedy J., Klein R. M. Developmental pattern of ventricular atrial natriuretic peptide (ANP) expression in chronically hypoxic rats as an indicator of the hypertrophic process. J Mol Cell Cardiol. 1994 Jun;26(6):753–767. doi: 10.1006/jmcc.1994.1090. [DOI] [PubMed] [Google Scholar]
  79. McMahon S. B., Monroe J. G. Role of primary response genes in generating cellular responses to growth factors. FASEB J. 1992 Jun;6(9):2707–2715. doi: 10.1096/fasebj.6.9.1612295. [DOI] [PubMed] [Google Scholar]
  80. Meldrum D. R. Tumor necrosis factor in the heart. Am J Physiol. 1998 Mar;274(3 Pt 2):R577–R595. doi: 10.1152/ajpregu.1998.274.3.R577. [DOI] [PubMed] [Google Scholar]
  81. Mercadier J. J., Bouveret P., Gorza L., Schiaffino S., Clark W. A., Zak R., Swynghedauw B., Schwartz K. Myosin isoenzymes in normal and hypertrophied human ventricular myocardium. Circ Res. 1983 Jul;53(1):52–62. doi: 10.1161/01.res.53.1.52. [DOI] [PubMed] [Google Scholar]
  82. Misao J., Hayakawa Y., Ohno M., Kato S., Fujiwara T., Fujiwara H. Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction. Circulation. 1996 Oct 1;94(7):1506–1512. doi: 10.1161/01.cir.94.7.1506. [DOI] [PubMed] [Google Scholar]
  83. Molkentin J. D., Lu J. R., Antos C. L., Markham B., Richardson J., Robbins J., Grant S. R., Olson E. N. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell. 1998 Apr 17;93(2):215–228. doi: 10.1016/s0092-8674(00)81573-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Morgan H. E., Baker K. M. Cardiac hypertrophy. Mechanical, neural, and endocrine dependence. Circulation. 1991 Jan;83(1):13–25. doi: 10.1161/01.cir.83.1.13. [DOI] [PubMed] [Google Scholar]
  85. Nakagawa T., Zhu H., Morishima N., Li E., Xu J., Yankner B. A., Yuan J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature. 2000 Jan 6;403(6765):98–103. doi: 10.1038/47513. [DOI] [PubMed] [Google Scholar]
  86. Narula J., Haider N., Virmani R., DiSalvo T. G., Kolodgie F. D., Hajjar R. J., Schmidt U., Semigran M. J., Dec G. W., Khaw B. A. Apoptosis in myocytes in end-stage heart failure. N Engl J Med. 1996 Oct 17;335(16):1182–1189. doi: 10.1056/NEJM199610173351603. [DOI] [PubMed] [Google Scholar]
  87. Nishida M., Springhorn J. P., Kelly R. A., Smith T. W. Cell-cell signaling between adult rat ventricular myocytes and cardiac microvascular endothelial cells in heterotypic primary culture. J Clin Invest. 1993 May;91(5):1934–1941. doi: 10.1172/JCI116412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Nishigaki K., Minatoguchi S., Seishima M., Asano K., Noda T., Yasuda N., Sano H., Kumada H., Takemura M., Noma A. Plasma Fas ligand, an inducer of apoptosis, and plasma soluble Fas, an inhibitor of apoptosis, in patients with chronic congestive heart failure. J Am Coll Cardiol. 1997 May;29(6):1214–1220. doi: 10.1016/s0735-1097(97)00055-7. [DOI] [PubMed] [Google Scholar]
  89. Olivetti G., Abbi R., Quaini F., Kajstura J., Cheng W., Nitahara J. A., Quaini E., Di Loreto C., Beltrami C. A., Krajewski S. Apoptosis in the failing human heart. N Engl J Med. 1997 Apr 17;336(16):1131–1141. doi: 10.1056/NEJM199704173361603. [DOI] [PubMed] [Google Scholar]
  90. Orkin S. H. GATA-binding transcription factors in hematopoietic cells. Blood. 1992 Aug 1;80(3):575–581. [PubMed] [Google Scholar]
  91. Orrenius S., Burgess D. H., Hampton M. B., Zhivotovsky B. Mitochondria as the focus of apoptosis research. Cell Death Differ. 1997 Aug;4(6):427–428. doi: 10.1038/sj.cdd.4400272. [DOI] [PubMed] [Google Scholar]
  92. Paradis P., MacLellan W. R., Belaguli N. S., Schwartz R. J., Schneider M. D. Serum response factor mediates AP-1-dependent induction of the skeletal alpha-actin promoter in ventricular myocytes. J Biol Chem. 1996 May 3;271(18):10827–10833. doi: 10.1074/jbc.271.18.10827. [DOI] [PubMed] [Google Scholar]
  93. Pennica D., King K. L., Shaw K. J., Luis E., Rullamas J., Luoh S. M., Darbonne W. C., Knutzon D. S., Yen R., Chien K. R. Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1142–1146. doi: 10.1073/pnas.92.4.1142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Pentel P. R., Jentzen J., Sievert J. Myocardial necrosis due to intraperitoneal administration of phenylpropanolamine in rats. Fundam Appl Toxicol. 1987 Jul;9(1):167–172. doi: 10.1016/0272-0590(87)90163-1. [DOI] [PubMed] [Google Scholar]
  95. Perennec J., Willemin M., Pocholle P., Hatt P. Y., Crozatier B. Cardiac ultrastructural abnormalities in Syrian hamsters with spontaneous cardiomyopathy or subjected to cardiac overloads. Basic Res Cardiol. 1992 Jan-Feb;87(1):54–64. doi: 10.1007/BF00795390. [DOI] [PubMed] [Google Scholar]
  96. Peters A., Liu E., Verrier R. L., Schwartz J., Gold D. R., Mittleman M., Baliff J., Oh J. A., Allen G., Monahan K. Air pollution and incidence of cardiac arrhythmia. Epidemiology. 2000 Jan;11(1):11–17. doi: 10.1097/00001648-200001000-00005. [DOI] [PubMed] [Google Scholar]
  97. Pfeffer M. A., Braunwald E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation. 1990 Apr;81(4):1161–1172. doi: 10.1161/01.cir.81.4.1161. [DOI] [PubMed] [Google Scholar]
  98. Piano M. R., Bondmass M., Schwertz D. W. The molecular and cellular pathophysiology of heart failure. Heart Lung. 1998 Jan-Feb;27(1):3–21. doi: 10.1016/s0147-9563(98)90063-2. [DOI] [PubMed] [Google Scholar]
  99. Piano M. R. Cellular and signaling mechanisms of cardiac hypertrophy. J Cardiovasc Nurs. 1994 Jul;8(4):1–26. doi: 10.1097/00005082-199407000-00003. [DOI] [PubMed] [Google Scholar]
  100. Pucéat M., Vassort G. Signalling by protein kinase C isoforms in the heart. Mol Cell Biochem. 1996 Apr 12;157(1-2):65–72. doi: 10.1007/BF00227882. [DOI] [PubMed] [Google Scholar]
  101. Pulkki K. J. Cytokines and cardiomyocyte death. Ann Med. 1997 Aug;29(4):339–343. doi: 10.3109/07853899708999358. [DOI] [PubMed] [Google Scholar]
  102. Rao A., Luo C., Hogan P. G. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol. 1997;15:707–747. doi: 10.1146/annurev.immunol.15.1.707. [DOI] [PubMed] [Google Scholar]
  103. Reed J. C., Jurgensmeier J. M., Matsuyama S. Bcl-2 family proteins and mitochondria. Biochim Biophys Acta. 1998 Aug 10;1366(1-2):127–137. doi: 10.1016/s0005-2728(98)00108-x. [DOI] [PubMed] [Google Scholar]
  104. Robbins J. Remodeling the cardiac sarcomere using transgenesis. Annu Rev Physiol. 2000;62:261–287. doi: 10.1146/annurev.physiol.62.1.261. [DOI] [PubMed] [Google Scholar]
  105. Rooney J. W., Hodge M. R., McCaffrey P. G., Rao A., Glimcher L. H. A common factor regulates both Th1- and Th2-specific cytokine gene expression. EMBO J. 1994 Feb 1;13(3):625–633. doi: 10.1002/j.1460-2075.1994.tb06300.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Rosen M. R. Cardiac arrhythmias and antiarrhythmic drugs: recent advances in our understanding of mechanism. J Cardiovasc Electrophysiol. 1995 Oct;6(10 Pt 2):868–879. doi: 10.1111/j.1540-8167.1995.tb00363.x. [DOI] [PubMed] [Google Scholar]
  107. Rozich J. D., Barnes M. A., Schmid P. G., Zile M. R., McDermott P. J., Cooper G., 4th Load effects on gene expression during cardiac hypertrophy. J Mol Cell Cardiol. 1995 Jan;27(1):485–499. doi: 10.1016/s0022-2828(08)80044-2. [DOI] [PubMed] [Google Scholar]
  108. Sabbah H. N., Sharov V. G. Apoptosis in heart failure. Prog Cardiovasc Dis. 1998 May-Jun;40(6):549–562. doi: 10.1016/s0033-0620(98)80003-0. [DOI] [PubMed] [Google Scholar]
  109. Sadoshima J., Izumo S. Signal transduction pathways of angiotensin II--induced c-fos gene expression in cardiac myocytes in vitro. Roles of phospholipid-derived second messengers. Circ Res. 1993 Sep;73(3):424–438. doi: 10.1161/01.res.73.3.424. [DOI] [PubMed] [Google Scholar]
  110. Sadoshima J., Qiu Z., Morgan J. P., Izumo S. Tyrosine kinase activation is an immediate and essential step in hypotonic cell swelling-induced ERK activation and c-fos gene expression in cardiac myocytes. EMBO J. 1996 Oct 15;15(20):5535–5546. [PMC free article] [PubMed] [Google Scholar]
  111. Sadoshima J., Xu Y., Slayter H. S., Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell. 1993 Dec 3;75(5):977–984. doi: 10.1016/0092-8674(93)90541-w. [DOI] [PubMed] [Google Scholar]
  112. Saikumar P., Dong Z., Patel Y., Hall K., Hopfer U., Weinberg J. M., Venkatachalam M. A. Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene. 1998 Dec 31;17(26):3401–3415. doi: 10.1038/sj.onc.1202590. [DOI] [PubMed] [Google Scholar]
  113. Sakai S., Miyauchi T., Kobayashi M., Yamaguchi I., Goto K., Sugishita Y. Inhibition of myocardial endothelin pathway improves long-term survival in heart failure. Nature. 1996 Nov 28;384(6607):353–355. doi: 10.1038/384353a0. [DOI] [PubMed] [Google Scholar]
  114. Sakai S., Miyauchi T., Sakurai T., Kasuya Y., Ihara M., Yamaguchi I., Goto K., Sugishita Y. Endogenous endothelin-1 participates in the maintenance of cardiac function in rats with congestive heart failure. Marked increase in endothelin-1 production in the failing heart. Circulation. 1996 Mar 15;93(6):1214–1222. doi: 10.1161/01.cir.93.6.1214. [DOI] [PubMed] [Google Scholar]
  115. Saraste A., Pulkki K., Kallajoki M., Henriksen K., Parvinen M., Voipio-Pulkki L. M. Apoptosis in human acute myocardial infarction. Circulation. 1997 Jan 21;95(2):320–323. doi: 10.1161/01.cir.95.2.320. [DOI] [PubMed] [Google Scholar]
  116. Scaffidi C., Fulda S., Srinivasan A., Friesen C., Li F., Tomaselli K. J., Debatin K. M., Krammer P. H., Peter M. E. Two CD95 (APO-1/Fas) signaling pathways. EMBO J. 1998 Mar 16;17(6):1675–1687. doi: 10.1093/emboj/17.6.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  117. Schaper J., Lorenz-Meyer S., Suzuki K. The role of apoptosis in dilated cardiomyopathy. Herz. 1999 May;24(3):219–224. doi: 10.1007/BF03044964. [DOI] [PubMed] [Google Scholar]
  118. Schneider P., Tschopp J. Apoptosis induced by death receptors. Pharm Acta Helv. 2000 Mar;74(2-3):281–286. doi: 10.1016/s0031-6865(99)00038-2. [DOI] [PubMed] [Google Scholar]
  119. Schwartz K., Boheler K. R., de la Bastie D., Lompre A. M., Mercadier J. J. Switches in cardiac muscle gene expression as a result of pressure and volume overload. Am J Physiol. 1992 Mar;262(3 Pt 2):R364–R369. doi: 10.1152/ajpregu.1992.262.3.R364. [DOI] [PubMed] [Google Scholar]
  120. Seta Y., Shan K., Bozkurt B., Oral H., Mann D. L. Basic mechanisms in heart failure: the cytokine hypothesis. J Card Fail. 1996 Sep;2(3):243–249. doi: 10.1016/s1071-9164(96)80047-9. [DOI] [PubMed] [Google Scholar]
  121. Sgonc R., Gruber J. Apoptosis detection: an overview. Exp Gerontol. 1998 Sep;33(6):525–533. doi: 10.1016/s0531-5565(98)00031-x. [DOI] [PubMed] [Google Scholar]
  122. Shan K., Kurrelmeyer K., Seta Y., Wang F., Dibbs Z., Deswal A., Lee-Jackson D., Mann D. L. The role of cytokines in disease progression in heart failure. Curr Opin Cardiol. 1997 May;12(3):218–223. doi: 10.1097/00001573-199705000-00002. [DOI] [PubMed] [Google Scholar]
  123. Sharov V. G., Sabbah H. N., Shimoyama H., Goussev A. V., Lesch M., Goldstein S. Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure. Am J Pathol. 1996 Jan;148(1):141–149. [PMC free article] [PubMed] [Google Scholar]
  124. Sheng Z., Knowlton K., Chen J., Hoshijima M., Brown J. H., Chien K. R. Cardiotrophin 1 (CT-1) inhibition of cardiac myocyte apoptosis via a mitogen-activated protein kinase-dependent pathway. Divergence from downstream CT-1 signals for myocardial cell hypertrophy. J Biol Chem. 1997 Feb 28;272(9):5783–5791. doi: 10.1074/jbc.272.9.5783. [DOI] [PubMed] [Google Scholar]
  125. Sheng Z., Pennica D., Wood W. I., Chien K. R. Cardiotrophin-1 displays early expression in the murine heart tube and promotes cardiac myocyte survival. Development. 1996 Feb;122(2):419–428. doi: 10.1242/dev.122.2.419. [DOI] [PubMed] [Google Scholar]
  126. Shier W. T., DuBourdieu D. J. Sodium- and calcium-dependent steps in the mechanism of neonatal rat cardiac myocyte killing by ionophores. I. The sodium-carrying ionophore, monensin. Toxicol Appl Pharmacol. 1992 Sep;116(1):38–46. doi: 10.1016/0041-008x(92)90142-f. [DOI] [PubMed] [Google Scholar]
  127. Sleight P. Calcium antagonists during and after myocardial infarction. Drugs. 1996 Feb;51(2):216–225. doi: 10.2165/00003495-199651020-00003. [DOI] [PubMed] [Google Scholar]
  128. Sonnenblick E. H., Anversa P. Models and remodeling: mechanisms and clinical implications. Cardiologia. 1999 Jul;44(7):609–619. [PubMed] [Google Scholar]
  129. Stemmer P. M., Klee C. B. Dual calcium ion regulation of calcineurin by calmodulin and calcineurin B. Biochemistry. 1994 Jun 7;33(22):6859–6866. doi: 10.1021/bi00188a015. [DOI] [PubMed] [Google Scholar]
  130. Sugden P. H., Clerk A. "Stress-responsive" mitogen-activated protein kinases (c-Jun N-terminal kinases and p38 mitogen-activated protein kinases) in the myocardium. Circ Res. 1998 Aug 24;83(4):345–352. doi: 10.1161/01.res.83.4.345. [DOI] [PubMed] [Google Scholar]
  131. Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol Rev. 1999 Jan;79(1):215–262. doi: 10.1152/physrev.1999.79.1.215. [DOI] [PubMed] [Google Scholar]
  132. Symanski J. D., Gettes L. S. Drug effects on the electrocardiogram. A review of their clinical importance. Drugs. 1993 Aug;46(2):219–248. doi: 10.2165/00003495-199346020-00002. [DOI] [PubMed] [Google Scholar]
  133. Tan Y., Rouse J., Zhang A., Cariati S., Cohen P., Comb M. J. FGF and stress regulate CREB and ATF-1 via a pathway involving p38 MAP kinase and MAPKAP kinase-2. EMBO J. 1996 Sep 2;15(17):4629–4642. [PMC free article] [PubMed] [Google Scholar]
  134. Tanaka M., Ito H., Adachi S., Akimoto H., Nishikawa T., Kasajima T., Marumo F., Hiroe M. Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes. Circ Res. 1994 Sep;75(3):426–433. doi: 10.1161/01.res.75.3.426. [DOI] [PubMed] [Google Scholar]
  135. Toraason M., Wey H. E., Richards D. E., Mathias P. I., Krieg E. Altered Ca2+ mobilization during excitation-contraction in cultured cardiac myocytes exposed to antimony. Toxicol Appl Pharmacol. 1997 Sep;146(1):104–115. doi: 10.1006/taap.1997.8198. [DOI] [PubMed] [Google Scholar]
  136. Torre-Amione G., Kapadia S., Benedict C., Oral H., Young J. B., Mann D. L. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol. 1996 Apr;27(5):1201–1206. doi: 10.1016/0735-1097(95)00589-7. [DOI] [PubMed] [Google Scholar]
  137. Torre-Amione G., Kapadia S., Lee J., Durand J. B., Bies R. D., Young J. B., Mann D. L. Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart. Circulation. 1996 Feb 15;93(4):704–711. doi: 10.1161/01.cir.93.4.704. [DOI] [PubMed] [Google Scholar]
  138. Vandenabeele P., Declercq W., Beyaert R., Fiers W. Two tumour necrosis factor receptors: structure and function. Trends Cell Biol. 1995 Oct;5(10):392–399. doi: 10.1016/s0962-8924(00)89088-1. [DOI] [PubMed] [Google Scholar]
  139. Wang J., Liu X., Arneja A. S., Dhalla N. S. Alterations in protein kinase A and protein kinase C levels in heart failure due to genetic cardiomyopathy. Can J Cardiol. 1999 Jun;15(6):683–690. [PubMed] [Google Scholar]
  140. Wang X. Z., Ron D. Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase. Science. 1996 May 31;272(5266):1347–1349. doi: 10.1126/science.272.5266.1347. [DOI] [PubMed] [Google Scholar]
  141. Wang Y., Huang S., Sah V. P., Ross J., Jr, Brown J. H., Han J., Chien K. R. Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family. J Biol Chem. 1998 Jan 23;273(4):2161–2168. doi: 10.1074/jbc.273.4.2161. [DOI] [PubMed] [Google Scholar]
  142. Weber K. T., Sun Y., Guarda E. Structural remodeling in hypertensive heart disease and the role of hormones. Hypertension. 1994 Jun;23(6 Pt 2):869–877. doi: 10.1161/01.hyp.23.6.869. [DOI] [PubMed] [Google Scholar]
  143. Wollert K. C., Heineke J., Westermann J., Lüdde M., Fiedler B., Zierhut W., Laurent D., Bauer M. K., Schulze-Osthoff K., Drexler H. The cardiac Fas (APO-1/CD95) Receptor/Fas ligand system : relation to diastolic wall stress in volume-overload hypertrophy in vivo and activation of the transcription factor AP-1 in cardiac myocytes. Circulation. 2000 Mar 14;101(10):1172–1178. doi: 10.1161/01.cir.101.10.1172. [DOI] [PubMed] [Google Scholar]
  144. Wollert K. C., Taga T., Saito M., Narazaki M., Kishimoto T., Glembotski C. C., Vernallis A. B., Heath J. K., Pennica D., Wood W. I. Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy. Assembly of sarcomeric units in series VIA gp130/leukemia inhibitory factor receptor-dependent pathways. J Biol Chem. 1996 Apr 19;271(16):9535–9545. doi: 10.1074/jbc.271.16.9535. [DOI] [PubMed] [Google Scholar]
  145. Wu C. F., Bishopric N. H., Pratt R. E. Atrial natriuretic peptide induces apoptosis in neonatal rat cardiac myocytes. J Biol Chem. 1997 Jun 6;272(23):14860–14866. doi: 10.1074/jbc.272.23.14860. [DOI] [PubMed] [Google Scholar]
  146. Wyllie A. H. Death from inside out: an overview. Philos Trans R Soc Lond B Biol Sci. 1994 Aug 30;345(1313):237–241. doi: 10.1098/rstb.1994.0099. [DOI] [PubMed] [Google Scholar]
  147. Yamamoto M., Ko L. J., Leonard M. W., Beug H., Orkin S. H., Engel J. D. Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes Dev. 1990 Oct;4(10):1650–1662. doi: 10.1101/gad.4.10.1650. [DOI] [PubMed] [Google Scholar]
  148. Yaoita H., Ogawa K., Maehara K., Maruyama Y. Apoptosis in relevant clinical situations: contribution of apoptosis in myocardial infarction. Cardiovasc Res. 2000 Feb;45(3):630–641. doi: 10.1016/s0008-6363(99)00349-1. [DOI] [PubMed] [Google Scholar]
  149. Yasue H., Yoshimura M., Sumida H., Kikuta K., Kugiyama K., Jougasaki M., Ogawa H., Okumura K., Mukoyama M., Nakao K. Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation. 1994 Jul;90(1):195–203. doi: 10.1161/01.cir.90.1.195. [DOI] [PubMed] [Google Scholar]
  150. Yin T., Sandhu G., Wolfgang C. D., Burrier A., Webb R. L., Rigel D. F., Hai T., Whelan J. Tissue-specific pattern of stress kinase activation in ischemic/reperfused heart and kidney. J Biol Chem. 1997 Aug 8;272(32):19943–19950. doi: 10.1074/jbc.272.32.19943. [DOI] [PubMed] [Google Scholar]
  151. Yoshibayashi M., Saito Y., Nakao K. Brain natriuretic peptide versus atrial natriuretic peptide--physiological and pathophysiological significance in children and adults: a review. Eur J Endocrinol. 1996 Sep;135(3):265–268. doi: 10.1530/eje.0.1350265. [DOI] [PubMed] [Google Scholar]
  152. de Oliveira C. F., Cintra K. A., Teixeira S. A., De Luca I. M., Antunes E., De Nucci G. Development of cardiomyocyte hypotrophy in rats under prolonged treatment with a low dose of a nitric oxide synthesis inhibitor. Eur J Pharmacol. 2000 Mar 10;391(1-2):121–126. doi: 10.1016/s0014-2999(99)00929-2. [DOI] [PubMed] [Google Scholar]

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