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Matrix Degradative Enzyme Activities on Cardiac Remodeling in Heart Failure

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Part of the book series: Progress in Experimental Cardiology ((PREC,volume 5))

Abstract

The development of congestive heart failure is associated with left ventricular dilation and myocardial remodeling. The matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP) activities play a significant role in extracellular remodeling. The inflammatory cytokine tumor necrosis factor-α (TNF-α) is proposed to affect myocardial remodeling and modulate myocyte cell growth and fibrosis. The synthesis of MMPs is also regulated by TNF-α in vitro study. However, it is not fully known that whether tissue TNF-α is associated with expressions for MMPs and TIMPs of infarcted myocardium in animal model.

Myocardial infarction (MI) was induced by surgical occlusion of the left main coronary artery in rats. Collagen content in infarcted tissues increased four folds at the first week after MI. In infarcted tissues, MMP-9 mRNA levels were early expressed within one week after MI. Those levels for MMP-13 and MMP-2 were both enhanced after from day 7 to day 14 and thereafter decreased at day 28. MMP-3 and MMP-14 mRNA expressions were expressed at day 14 and 28 after MI. The levels of TIMP-1 and TIMP-2 mRNA expression were elevated within one week and thereafter reduced. TIMP-3 mRNA expression was greater from day 14. TNF-α mRNA in the infarcted tissues increased within one week and those levels were still elevated by day 14. By the Western blotting and immunostaining studies, the maximal TNF-α protein levels were observed on day 7 in the infarcted tissues where large numbers of macrophage were infiltrated. Thus, MMP-9 was co-expressed with TNF-α at an early phase after MI. Other MMPs were more expressed after one week. We suggest that ventricular remodeling in infarcted tissue may be initially contributed to the enhancement of TNF-α expression, which can increase MMPs activity in cardiac fibroblasts.

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Makino, N., Sugano, M., Masutomo, K., Hata, T., Fushiki, S. (2003). Matrix Degradative Enzyme Activities on Cardiac Remodeling in Heart Failure. In: Singal, P.K., Dixon, I.M.C., Kirshenbaum, L.A., Dhalla, N.S. (eds) Cardiac Remodeling and Failure. Progress in Experimental Cardiology, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9262-8_21

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  • DOI: https://doi.org/10.1007/978-1-4419-9262-8_21

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4864-1

  • Online ISBN: 978-1-4419-9262-8

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