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Am J Physiol Heart Circ Physiol 294: H1815-H1822, 2008. First published February 8, 2008; doi:10.1152/ajpheart.00831.2007
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Age-related differences in postinfarct left ventricular rupture and remodeling

Yining Yang,1 Yitong Ma,1 Wei Han,1 Jun Li,1 Yang Xiang,1 Fen Liu,1 Xiang Ma,1 JianFa Zhang,1 Zhenyan Fu,1 Yi-Dan Su,2 Xiao-Jun Du,2 and Xiao-Ming Gao2

1Cardiovascular Research Institute, Xinjiang Medical University, Xinjiang, China; and 2Baker Heart Research Institute, Melbourne, Australia

Submitted 17 July 2007 ; accepted in final form 2 February 2008

Cardiac rupture is more prevalent in elderly patients with first onset of acute myocardial infarct (MI), but the mechanism remains unexplored. We investigated the differences in the incidence of cardiac rupture and early left ventricular (LV) remodeling following coronary artery ligation between old (12-mo) and young (3-mo) C57Bl/6 male mice and explored responsible mechanisms. The incidence of rupture within 1 wk after MI was significantly higher in old than in young mice (40.7 vs. 18.3%, P = 0.013) despite a similar infarct size in both age groups. Old mice dying of rupture had more severe infarct expansion than young counterparts. Echocardiography and catheterization at day 7 revealed more profound LV chamber dilatation and dysfunction as well as higher blood pressures in aged mice. At day 3 after MI immediately before the peak of rupture occurrence, we observed significantly higher content of type I and III collagen, a greater density of macrophage and neutrophil, and markedly enhanced mRNA expression of inflammatory cytokines in the infarcted myocardium in old than in young mice. Furthermore, a more dramatic increment of matrix metalloproteinase (MMP)-9 activity was found in old than in young infarcted hearts, in keeping with enhanced inflammatory response. Collectively, these results revealed that old mice had a higher risk of post-MI cardiac rupture despite a higher level of collagen content and cross-linking. Enhanced inflammatory response and subsequent increase in MMP-9 activity together with higher blood pressure are important factors responsible for the higher risk of cardiac rupture and more severe LV remodeling in the aged heart following acute MI.

infarct expansion; collagen; matrix metalloproteinase; inflammatory cytokines



Address for reprint requests and other correspondence: X.-M. Gao, Baker Heart Research Institute, P. O. Box 6492, St. Kilda Rd., Melbourne, 8008, Australia (e-mail: xiaoming.gao{at}baker.edu.au)




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