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特发性扩张型心肌病中基质金属蛋白酶表达与左心室功能的关联

Association of matrix metalloproteinase expression and left ventricular function in idiopathic dilated cardiomyopathy.

作者信息

Yokoseki O, Yazaki Y, Suzuki J, Imamura H, Takenaka H, Isobe M

机构信息

First Department of Internal Medicine, Shinshu University, School of Medicine, Matsumoto, Japan.

出版信息

Jpn Circ J. 2000 May;64(5):352-7. doi: 10.1253/jcj.64.352.

Abstract

Myocardial remodeling is an important predictor for the development of dilated cardiomyopathy (DCM). Matrix metalloproteinases (MMPs) are the family of proteins responsible for extracellular remodeling, and tissue inhibitors of metalloproteinases (TIMPs) tightly control their activity. In the present study, the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 was determined by immunohistochemistry in right ventricular endomyocardial biopsy samples from 16 patients with idiopathic DCM, and its clinical significance was evaluated by comparison with parameters of cardiac function. To obtain a semi-quantitative assessment of MMP and TIMP expression, the average number of positive cells per high power field was counted. The left ventricular ejection fraction (LVEF) significantly correlated with the expression of both MMP-2 (r=-0.68) and TIMP-2 (r=-0.58). Patients were classified into 2 groups according to the degree of MMP-2 expression: strongly positive and weakly positive. LVEF, left ventricular (LV) end-diastolic pressure, right ventricular end-diastolic pressure, pulmonary capillary wedge pressure and the plasma norepinephrine level were significantly greater in the strongly positive group (p<0.05). In conclusion, the expression of MMPs and TIMPs in the cardiac matrix of patients with idiopathic DCM is closely associated with myocardial remodeling and subsequent deterioration of LV performance. These findings suggest new therapeutic targets for patients with idiopathic DCM.

摘要

心肌重塑是扩张型心肌病(DCM)发生发展的重要预测指标。基质金属蛋白酶(MMPs)是负责细胞外重塑的蛋白质家族,而金属蛋白酶组织抑制剂(TIMPs)则严格控制其活性。在本研究中,采用免疫组织化学法测定了16例特发性DCM患者右心室心内膜活检样本中MMP-2、MMP-9、TIMP-1和TIMP-2的表达,并通过与心功能参数比较评估其临床意义。为了对MMP和TIMP表达进行半定量评估,计算每个高倍视野阳性细胞的平均数。左心室射血分数(LVEF)与MMP-2(r=-0.68)和TIMP-2(r=-0.58)的表达均显著相关。根据MMP-2表达程度将患者分为两组:强阳性组和弱阳性组。强阳性组的LVEF、左心室(LV)舒张末期压力、右心室舒张末期压力、肺毛细血管楔压和血浆去甲肾上腺素水平均显著更高(p<0.05)。总之,特发性DCM患者心脏基质中MMPs和TIMPs的表达与心肌重塑及随后的左心室功能恶化密切相关。这些发现为特发性DCM患者提供了新的治疗靶点。

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