Boixel Christophe, Fontaine Vincent, Rücker-Martin Catherine, Milliez Paul, Louedec Liliane, Michel Jean Baptiste, Jacob Marie Paule, Hatem Stéphane N
INSERM Unité 460, Paris, France.
J Am Coll Cardiol. 2003 Jul 16;42(2):336-44. doi: 10.1016/s0735-1097(03)00578-3.
The purpose of this study was to determine the pathogenic factors and molecular mechanisms involved in fibrosis of the atria.
Fibrosis is an important component of the pathophysiology of atrial fibrillation, especially when the arrhythmia is associated with heart failure (HF) or atrial dilation.
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.
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.
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.
本研究旨在确定心房纤维化的致病因素及分子机制。
纤维化是心房颤动病理生理学的重要组成部分，尤其是当心律失常与心力衰竭（HF）或心房扩张相关时。
我们使用心肌梗死（MI）合并不同程度左心室功能障碍和心房扩张的大鼠模型，通过组织学、蛋白质印迹、酶谱分析和免疫组织学技术研究左心房（LA）心肌的纤维化和基质金属蛋白酶（MMP）活性。
左冠状动脉手术结扎3个月后，27只大鼠发生大面积心肌梗死，12只处于轻度心力衰竭，15只处于重度心力衰竭。两组在超声心动图检查中均有左心房扩大。组织切片的Masson三色染色和苦味酸天狼星染色显示，在轻度和重度心力衰竭中，小梁周围以及溶解的心肌细胞周围均有明显纤维化。在轻度心力衰竭中，基质溶素MMP-7的活性和表达增加（122%），而在重度心力衰竭中，MMP-7（211%）和明胶酶MMP-2（187%）均上调。MMP抑制剂TIMP-1、-2和-4的表达或活性没有变化。冰冻切片的免疫染色显示，MMP-2存在于间质间隙，而MMP-7在溶解的心肌细胞中积聚。
心房血流动力学过载是纤维化的重要致病因素；MMP-7似乎参与了这一组织重塑过程的早期阶段。
