Matrix metalloproteinase expression in nonrheumatic aortic stenosis
Matrix metalloproteinase expression in nonrheumatic aortic stenosis
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DOI：
10.1016/s1054-8807(00)00043-0
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发表时间：
2000-09-01
影响因子：
3.7
通讯作者：
Brown, DL
中科院分区：
文献类型：
--
作者：
Edep, ME;Shirani, J;Brown, DL
背景：非风湿性主动脉瓣狭窄（NAS）被认为是一种退行性病变，其特征为瓣膜增厚、纤维钙化团块、胶原紊乱以及炎性浸润。基质金属蛋白酶（MMPs）是由炎性细胞产生的一族依赖锌和钙的酶，能够降解胶原、弹性蛋白和蛋白聚糖。本研究旨在验证MMPs参与NAS发病机制这一假说。
方法与结果：从9例接受瓣膜置换的NAS患者和4例尸检时无NAS的患者获取主动脉瓣。对NAS标本的显微镜分析显示，钙沉积、纤维化区域各异，且有大量由巨噬细胞、淋巴细胞和成纤维细胞组成的细胞浸润。对照主动脉瓣结构正常，以成纤维细胞为主，偶见散在的巨噬细胞，无淋巴细胞。用抗MMP - 1、 - 2、 - 3和 - 9的抗体进行免疫组化染色，结果显示所有NAS患者的巨噬细胞、淋巴细胞和成纤维细胞中均有每种酶的表达。正常瓣膜中的固有成纤维细胞和巨噬细胞表达MMP - 1、 - 2和 - 3，但程度较轻。在正常瓣膜中未检测到MMP - 9。
结论：本研究证实NAS中存在由巨噬细胞和淋巴细胞组成的炎性浸润。此外，还记录到NAS瓣膜叶中MMP - 1、 - 2和 - 3表达增加以及MMP - 9的独特表达。这些发现与NAS与慢性炎症相关以及MMPs表达增加可能促成这一疾病过程的发病机制这一假说相符。《心血管病理学》2000年；9：281 - 286（C）2000年，爱思唯尔科学公司出版
Background: Nonrheumatic aortic stenosis (NAS) is considered to be a degenerative process characterized by valve thickening, fibrocalcific masses, collagen disarray, and an inflammatory infiltrate. The matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent enzymes produced by inflammatory cells that are capable of degrading collagen, elastin, and proteoglycans. This study sought to test the hypothesis that MMPs are involved in the pathogenesis of NAS. Methods and Results: Aortic values were obtained from nine patients with NAS undergoing valve replace ment and from four patients without NAS during autopsy. Microscopic analysis of NAS specimens revealed variable areas of calcium deposits, fibrosis, and an extensive cellular infiltrate consisting of macrophages, lymphocytes, and fibroblasts. Control aortic valves demonstrated normal architecture, a predominance of fibroblasts, occasional scattered macrophages, and no lymphocytes. Immunohistochemical staining with antibodies to MMP-1, -2, -3 and -9 revealed expression of each enzyme in macrophages, lymphocytes, and fibroblasts of all NAS patients. MMP-1; -2 and -3 were expressed by resident fibroblasts and macrophages in normal valves, but to a lesser degree. Tc MMP-9 was not identified in normal valves. Conclusions: The current study confirms an inflammatory infiltrate composed of macrophages and lymphocytes in NAS. Additionally, the increased expression of MMP-1, -2, and -3, along with the unique expression of MMP-9 in NAS valve leaflets was documented. These findings are consistent with the hypothesis that NAS is associated with chronic inflammation and that the increased expression of MMPs may contribute to the pathogenesis of this disease process. Cardiovasc Pathol 2000;9:281-286 (C) 2000 by Elsevier Science Inc.