Overexpression of elastin fragments in infarcted myocardium attenuates scar expansion and heart dysfunction
Overexpression of elastin fragments in infarcted myocardium attenuates scar expansion and heart dysfunction
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DOI：
10.1152/ajpheart.00862.2004
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发表时间：
2005-06-01
影响因子：
4.8
通讯作者：
Li, RK
中科院分区：
文献类型：
--
作者：
Mizuno, T;Mickle, DAG;Li, RK
心肌梗死后心室扩张可导致心力衰竭。增加梗死区的强度和弹性可能会阻止心室扩张。由于弹性蛋白为组织提供强度、延展性和弹性并维持组织结构，我们研究了梗死中弹性蛋白表达对瘢痕扩张和心脏功能的影响。将用具有弹性蛋白基因片段的质粒或载体转染的COS-7细胞接种到Gelfoam网中并培养。机械拉伸试验（n = 5/组）显示，弹性蛋白补片的弹性（P <0.05）和拉伸（P <0.05）均高于向量补片。在大鼠体内研究中，在冠状动脉左前降支结扎后6天，将COS-7细胞（Cell组，n = 7）或具有弹性蛋白基因的COS-7细胞（Elastin组，n = 9）或载体（Vector组，n = 9）移植到梗死区;梗死大鼠作为对照（n = 7）。超过8周，细胞组与对照组相比没有表现出对瘢痕扩张和心脏功能恶化的影响。相比之下，Elastin组与Vector组相比，梗死范围更小，心功能更好地维持（P <0.05）。细胞移植后8 wk，Langendorff数据显示Elastin组较Vector组有更大（P <0.01）的发展压力和更小的左心室容积。Western blot和组织学检查显示Elastin组梗死灶内有弹性蛋白积聚。通过增加弹性蛋白片段含量改变心肌梗死的细胞外基质组成可减弱瘢痕扩张、心室扩张和心功能不全的发生。
Ventricular dilation after myocardial infarction can cause heart failure. Increasing strength and elasticity in the infarct region might prevent ventricular dilation. Because elastin provides strength, extensibility, and resilience to tissues and maintains tissue architecture, we studied the effect of elastin expression in the infarct on scar expansion and heart function. COS-7 cells transfected with a plasmid with an elastin gene fragment or a vector were seeded into a Gelfoam mesh and cultured. Mechanical stretch test ( n = 5/group) showed that the elastin mesh was more elastic ( P < 0.05) and tensile ( P < 0.05) than the vector mesh. In an in vivo study in rats, 6 days after left anterior descending coronary artery ligation, COS-7 cells ( Cell group, n = 7) or COS-7 cells with elastin gene ( Elastin group, n = 9) or vector ( Vector group, n = 9) were transplanted into the infarct; infarcted rats served as controls ( n = 7). Over 8 wk the Cell group did not demonstrate effects on scar expansion and deterioration of heart function vs. controls. In contrast, infarct expansion was smaller and heart function was better maintained in the Elastin group vs. the Vector group ( P < 0.05). At 8 wk after cell transplantation Langendorff data showed that the Elastin group had greater ( P < 0.01) developed pressure and a smaller left ventricular volume than the Vector group. Western blot and histology showed accumulated elastin in the Elastin group infarct. Changing the extracellular matrix composition of a myocardial infarct by increasing elastin fragment content attenuated scar expansion, ventricular dilation, and onset of heart dysfunction.