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From the Department of Cardiovascular Medicine, Kyoto University,
Graduate School of Medicine, Kyoto, Japan.
Correspondence to Akira Matsumori, MD, PhD, Department of Cardiovascular Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-Ku, Kyoto 606, Japan.
Background—A large transmural
myocardial infarction may initiate structural and geometric changes in
the left ventricle that are commonly referred to as remodeling.
Progressive, adverse remodeling of the myocardium may lead
to ventricular dilatation and congestive heart failure.
Recent studies have highlighted the effects of some cytokines
on immune-mediated myocyte injury, postischemic myocardial
inflammation, and cardiac function. However, studies of the involvement
of cytokines in remodeling of the heart are few.
Methods and Results—In a rat model of myocardial infarction,
progressive dilatation of the left ventricular cavity and
lack of appropriate hypertrophy of the surviving
myocardium were confirmed by transthoracic
echocardiography. The relative expression of mRNA
for tumor necrosis factor (TNF)-
Conclusions—These findings suggest the possible involvement of
cytokines during the remodeling process of the noninfarcted
left ventricular myocardium.
© 1998 American Heart Association, Inc.
Basic Science Reports
Cytokine Gene Expression After Myocardial Infarction in Rat Hearts
Possible Implication in Left Ventricular Remodeling
, interleukin (IL)-1ß, and IL-6 in
the infarcted and noninfarcted myocardium of these rats, as
well as in a group of sham-operated animals, was assessed by the
technique of quantitative polymerase chain reaction amplification. In
the infarcted region, TNF-, IL-1ß, and IL-6 gene expression peaked
at 1 week after infarction and decreased rapidly thereafter. In
contrast, at 20 weeks after infarction, the gene expression levels of
these cytokines remained significantly higher in the
noninfarcted than in the infarcted zone or in the
myocardium of sham-operated animals. Furthermore, the
levels of these cytokines in the noninfarcted region correlated
with the left ventricular end-diastolic
diameter measured at 8 and 20 weeks after infarction. Among these
cytokines, IL-1ß expression was highest, and its
level correlated well with collagen deposition in the noninfarcted
myocardium at 8 and 20 weeks after surgery. At 20 weeks
after infarction, immunohistochemical analysis revealed the
presence of IL-1ß in macrophages, endothelial
cells, and vascular smooth muscle cells in the noninfarcted region,
whereas no such immunoreactivity was found in the
myocardium of sham-operated animals.
Key Words: cytokines • remodeling • myocardial infarction • immunohistochemistry
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A. Burger, M. Benicke, A. Deten, and H.-G. Zimmer Catecholamines stimulate interleukin-6 synthesis in rat cardiac fibroblasts Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H14 - H21. [Abstract] [Full Text] [PDF]
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J. P. Loennechen, A. Stoylen, V. Beisvag, U. Wisloff, and O. Ellingsen Regional expression of endothelin-1, ANP, IGF-1, and LV wall stress in the infarcted rat heart Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2902 - H2910. [Abstract] [Full Text] [PDF]
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K. Abe, M. Tokumura, T. Ito, T. Murai, A. Takashima, and N. Ibii Involvement of iNOS in postischemic heart dysfunction of stroke-prone spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H668 - H673. [Abstract] [Full Text] [PDF]
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J. K. Damas, H. G. Eiken, E. Oie, V. Bjerkeli, A. Yndestad, T. Ueland, T. Tonnessen, O. R. Geiran, H. Aass, S. Simonsen, et al. Myocardial expression of CC- and CXC-chemokines and their receptors in human end-stage heart failure Cardiovasc Res, September 1, 2000; 47(4): 778 - 787. [Abstract] [Full Text] [PDF]
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D. A. Siwik, D. L.-F. Chang, and W. S. Colucci Interleukin-1{beta} and Tumor Necrosis Factor-{alpha} Decrease Collagen Synthesis and Increase Matrix Metalloproteinase Activity in Cardiac Fibroblasts In Vitro Circ. Res., June 23, 2000; 86(12): 1259 - 1265. [Abstract] [Full Text] [PDF]
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E. Oie, R. Bjornerheim, O. P. F. Clausen, and H. Attramadal Cyclosporin A inhibits cardiac hypertrophy and enhances cardiac dysfunction during postinfarction failure in rats Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H2115 - H2123. [Abstract] [Full Text] [PDF]
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L. W. Stanton, L. J. Garrard, D. Damm, B. L. Garrick, A. Lam, A. M. Kapoun, Q. Zheng, A. A. Protter, G. F. Schreiner, and R. T. White Altered Patterns of Gene Expression in Response to Myocardial Infarction Circ. Res., May 12, 2000; 86(9): 939 - 945. [Abstract] [Full Text] [PDF]
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S. D. Prabhu, B. Chandrasekar, D. R. Murray, and G. L. Freeman {beta}-Adrenergic Blockade in Developing Heart Failure : Effects on Myocardial Inflammatory Cytokines, Nitric Oxide, and Remodeling Circulation, May 2, 2000; 101(17): 2103 - 2109. [Abstract] [Full Text] [PDF]
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N. Nagaya, T. Nishikimi, F. Yoshihara, T. Horio, A. Morimoto, and K. Kangawa Cardiac adrenomedullin gene expression and peptide accumulation after acute myocardial infarction in rats Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2000; 278(4): R1019 - R1026. [Abstract] [Full Text] [PDF]
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M. Nakamura, N.-P. Wang, Z.-Q. Zhao, J. N Wilcox, V. Thourani, R. A Guyton, and J. Vinten-Johansen Preconditioning decreases Bax expression, PMN accumulation and apoptosis in reperfused rat heart Cardiovasc Res, February 1, 2000; 45(3): 661 - 670. [Abstract] [Full Text] [PDF]
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E. Isenovic and M. C. LaPointe Role of Ca2+-Independent Phospholipase A2 in the Regulation of Inducible Nitric Oxide Synthase in Cardiac Myocytes Hypertension, January 1, 2000; 35(1): 249 - 254. [Abstract] [Full Text] [PDF]
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M. Azzawi and P. Hasleton Tumour necrosis factor alpha and the cardiovascular system: its role in cardiac allograft rejection and heart disease Cardiovasc Res, September 1, 1999; 43(4): 850 - 859. [Full Text] [PDF]
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D. Gurantz, R. T. Cowling, F. J. Villarreal, and B. H. Greenberg Tumor Necrosis Factor-{alpha} Upregulates Angiotensin II Type 1 Receptors on Cardiac Fibroblasts Circ. Res., August 6, 1999; 85(3): 272 - 279. [Abstract] [Full Text] [PDF]
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S. Sasayama, A. Matsumori, and Y. Kihara New insights into the pathophysiological role for cytokines in heart failure Cardiovasc Res, June 1, 1999; 42(3): 557 - 564. [Full Text] [PDF]
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J. M.B Pinto and P. A Boyden Electrical remodeling in ischemia and infarction Cardiovasc Res, May 1, 1999; 42(2): 284 - 297. [Abstract] [Full Text] [PDF]
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 A. Liebold, C. Keyl, and D. E. Birnbaum The heart produces but the lungs consume proinflammatory cytokines following cardiopulmonary bypass Eur. J. Cardiothorac. Surg., March 1, 1999; 15(3): 340 - 345. [Abstract] [Full Text] [PDF]
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N. A. Trueblood, Z. Xie, C. Communal, F. Sam, S. Ngoy, L. Liaw, A. W. Jenkins, J. Wang, D. B. Sawyer, O. H. L. Bing, et al. Exaggerated Left Ventricular Dilation and Reduced Collagen Deposition After Myocardial Infarction in Mice Lacking Osteopontin Circ. Res., May 25, 2001; 88(10): 1080 - 1087. [Abstract] [Full Text] [PDF]
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F. Sam, D. B. Sawyer, Z. Xie, D. L.F. Chang, S. Ngoy, D. A. Brenner, D. A. Siwik, K. Singh, C. S. Apstein, and W. S. Colucci Mice Lacking Inducible Nitric Oxide Synthase Have Improved Left Ventricular Contractile Function and Reduced Apoptotic Cell Death Late After Myocardial Infarction Circ. Res., August 17, 2001; 89(4): 351 - 356. [Abstract] [Full Text] [PDF]
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