Age-related differences in postinfarct left ventricular rupture and remodeling
Age-related differences in postinfarct left ventricular rupture and remodeling
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DOI：
10.1152/ajpheart.00831.2007
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发表时间：
2008-04-01
影响因子：
4.8
通讯作者：
Gao, Xiao-Ming
中科院分区：
文献类型：
--
作者：
Yang, Yining;Ma, Yitong;Gao, Xiao-Ming
心脏破裂在首次发作急性心肌梗塞（MI）的老年患者中更为常见，但其机制仍待探索。我们研究了老年（12 个月）和年轻（3 个月）C57B1/6 雄性小鼠之间冠状动脉结扎后心脏破裂和早期左心室 (LV) 重塑发生率的差异，并探讨了相关机制。尽管两个年龄组的梗死面积相似，但老年小鼠心肌梗塞后 1 周内的破裂发生率显着高于年轻小鼠（40.7% vs. 18.3%，P = 0.013）。死于破裂的老年小鼠比年轻小鼠有更严重的梗塞扩张。第 7 天的超声心动图和导管插入术显示老年小鼠有更严重的左心室扩张和功能障碍以及更高的血压。心肌梗死后第3天，在破裂发生高峰之前，我们观察到老年小鼠梗死心肌中I型和III型胶原的含量显着升高，巨噬细胞和中性粒细胞密度更高，炎症细胞因子的mRNA表达显着增强。此外，老年梗塞心脏中的基质金属蛋白酶（MMP）-9 活性比年轻的梗塞心脏有更显着的增加，这与炎症反应的增强相一致。总的来说，这些结果表明，尽管老年小鼠的胶原蛋白含量和交联水平较高，但心肌梗死后心脏破裂的风险较高。炎症反应增强、随后 MMP-9 活性增加以及血压升高是导致急性心肌梗死后老年心脏心脏破裂风险更高和左室重构更严重的重要因素。
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) C57B1/6 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.