Fibrosis of the left atria during progression of heart failure is associated with increased matrix metalloproteinases in the rat
Fibrosis of the left atria during progression of heart failure is associated with increased matrix metalloproteinases in the rat
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DOI：
10.1016/s0735-1097(03)00578-3
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发表时间：
2003-07-16
影响因子：
24
通讯作者：
Hatem, SN
中科院分区：
文献类型：
--
作者：
Boixel, C;Fontaine, V;Hatem, SN
目的本研究的目的是确定心房纤维化的致病因素和分子机制。背景：纤维化是心房颤动病理生理的重要组成部分，特别是当心律失常与心力衰竭或心房扩张相关时。方法采用组织学、Western blot、酶学、免疫组织学等方法，对心肌梗死（MI）合并不同程度左心室功能障碍和心房扩张的大鼠模型左房（LA）心肌纤维化及基质金属蛋白酶（MMP）活性进行研究。结果左冠状动脉结扎术后3个月，心肌梗死大鼠27只，轻度HF 12只，重度HF 15只。两组超声心动图均可见LA增大。马氏三色和小黑素染色显示，在轻度和重度HF患者，小梁周围和溶肌细胞周围均有明显的纤维化。在轻度HF中，基质溶素MMP-7的活性和表达增加（122%），而在重度HF中，MMP-7（211%）和明胶酶MMP-2（187%）均上调。MMP抑制剂TIMP-1、-2和-4的表达和活性均无变化。冷冻切片免疫染色显示间质中存在MMP-2，而溶肌细胞中存在MMP-7。结论：心房血流动力学超载是纤维化的重要致病因素；MMP-7似乎参与了这种组织重塑过程的早期阶段。(C) 2003年由美国心脏病学会基金会发布。
OBJECTIVES The purpose of this study was to determine the pathogenic factors and molecular mechanisms involved in fibrosis of the atria.BACKGROUND Fibrosis is an important component of the pathophysiology of atrial fibrillation, especially when the arrhythmia is associated with heart failure (HF) or atrial dilation.METHODS We used a rat model of myocardial infarction (MI) complicated by various degrees of left ventricular dysfunction and atrial dilation to study fibrosis and matrix metalloproteinase (MMP) activity in the left atrial (LA) myocardium by means of histologic, Western blot, zymographic, and immunohistologic techniques.RESULTS Three months after surgical ligature of the left coronary artery, 27 rats had a large MI, 12 were in mild HF, and 15 in severe HF. Both groups had LA enlargement at the echocardiography. Masson's trichrome and picrosirius staining of tissue sections revealed marked fibrosis at the periphery of trabeculae and also surrounding myolytic myocytes, in both mild and severe HF. In mild HF, the activity and expression of the matrilysin MMP-7 were increased (122%), whereas in severe HF, both MMP-7 (211%) and the gelatinase MMP-2 (187%) were up-regulated. There were no changes in the expression or activity of MMP inhibitors, TIMP-1, -2, and -4. Immunostaining of cryosections showed that MMP-2 was present in the interstitial spaces, whereas MMP-7 accumulated in myolytic myocytes.CONCLUSIONS Hemodynamic overload of the atria is an important pathogenic factor of fibrosis; MMP-7 appears to be involved in the early stage of this tissue remodeling process. (C) 2003 by the American College of Cardiology Foundation.