Elastin stabilizes an infarct and preserves ventricular function
Elastin stabilizes an infarct and preserves ventricular function
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DOI：
10.1161/circulationaha.105.523795
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发表时间：
2005-08-30
期刊：
影响因子：
37.8
通讯作者：
Li, RK
中科院分区：
文献类型：
--
作者：
Mizuno, T;Yau, TM;Li, RK
背景：心肌梗死后，如果心室壁缺乏弹性，损伤区域纤维化，心肌瘢痕可能扩大。心脏扩张可能加速进行性心力衰竭的恶性循环。本研究评估了使用细胞基因疗法在心肌瘢痕中增加弹性蛋白的功能益处。方法与结果：采用左前降支结扎法致大鼠心肌梗死。6天后，将转染大鼠弹性蛋白基因（弹性蛋白组，n= 14）或空质粒（对照组，n= 14）的22x 10(6)个同基因大鼠内皮细胞移植到梗死瘢痕内。通过超声心动图、Langendorff测量仪和平面测量仪监测心功能、左室（LV）体积和梗死面积3个月。采用Western blot法和组织学检查观察细胞和梗死区弹性蛋白沉积情况。细胞移植后3个月，弹性蛋白组瘢痕组织中出现重组弹性蛋白，对照组未见重组弹性蛋白。组织学检查显示梗死区有组织的弹性纤维。左室容积和梗死面积明显小于对照组(P
Background-After a myocardial infarction, the injured region becomes fibrotic and the myocardial scar may expand if the ventricular wall lacks elasticity. Cardiac dilatation may precipitate the vicious cycle of progressive heart failure. The present study evaluated the functional benefits of increasing elastin within a myocardial scar using cell based gene therapy. Methods andResults-A myocardial infarction was generated by ligation of the left anterior descending artery in rats. Six days later, 2X 10(6) syngeneic rat endothelial cells transfected with the rat elastin gene (elastin group, n= 14) or an empty plasmid (control group, n = 14) were transplanted into the infarct scar. Cardiac function, left ventricular (LV) volume, and infarct size were monitored over 3 months by echocardiography, Langendorff measurements, and planimetry. Elastin deposition was evaluated in the cells and in the infarct region by Western blot assay and by histological examination. Recombinant elastin was found in the scar in the elastin group but not the control group during the 3 months after cell transplantation. Histological assessment demonstrated organized elastic fibers within the infarct region. LV volume and infarct size were significantly smaller (P