Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis
Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis
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DOI：
10.1016/s0021-9150(03)00284-3
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发表时间：
2003-10-01
期刊：
影响因子：
5.3
通讯作者：
Borggrefe, M
中科院分区：
文献类型：
--
作者：
Kaden, JJ;Dempfle, CE;Borggrefe, M
钙化性主动脉瓣狭窄（AS）是老年人的主要心脏瓣膜疾病，其特征是细胞外基质广泛重塑。基质金属蛋白酶（MMPs）在钙化性AS中上调，并可能调节基质重塑。监管机制尚不明确。近年来的研究表明钙化性AS可能是由白细胞浸润和激活的炎症过程引起的，本研究旨在阐明促炎细胞因子白细胞介素（IL）-1 β对人主动脉瓣MMP表达和细胞增殖的作用。对瓣膜置换术或尸检时获得的有（n=6）和无（n =6）钙化的主动脉瓣进行白细胞、IL-1 β和MMP-1的免疫组织化学。狭窄瓣膜显示明显的白细胞浸润和相关的IL-1 β和MMP-1表达。在对照瓣膜中，仅存在散在的白细胞，MMP-1的低染色和IL-1 β的无染色。双标记免疫组化显示IL-1 β主要表达于白细胞，MMP-1主要表达于肌成纤维细胞。用IL-1 β刺激培养的人主动脉瓣肌成纤维细胞，通过Western blotting和酶谱分析，MMP-1和MMP-2的表达呈时间依赖性增加，而MMP-9保持不变。通过溴脱氧尿苷掺入测定，IL-1 β可增加细胞增殖。因此，IL-1 β可能调节钙化性AS细胞外基质的重塑。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
Calcific aortic valve stenosis (AS), the main heart valve disease in the elderly, is characterized by extensive remodeling of the extracellular matrix. Matrix metalloproteinases (MMPs) are upregulated in calcific AS and might modulate matrix remodeling. The regulatory mechanisms are unclear. As recent studies have suggested that calcific AS might result from an inflammatory process involving leukocyte invasion and activation, the present study aimed to elucidate the role of the pro-inflammatory cytokine interleukin (IL)- 1beta on MMP expression and cell proliferation in human aortic valves. Immunohistochemistry for leukocytes, IL-1beta and MMP-1 was performed on aortic valves with (n=6) and without (n=6) calcification obtained at valve replacement or autopsy. Stenotic valves showed marked leukocyte infiltration and associated expression of IL-1beta and MMP-1. In control valves only scattered leukocytes, low staining for MMP-1 and no staining for IL-1beta were present. Double-label immunostaining localized IL-1beta expression mainly to leukocytesandMMP-1 expression to myofibroblasts. Stimulation of cultured human aortic valve myofibroblasts with IL-1beta lead to a time-dependently increased expression of MMP- I and MMP-2 by Western blotting and zymography, whereas MMP-9 remained unchanged. Cell proliferation was increased by IL-1beta as determined by bromodesoxyuridine incorporation. Thus, IL-1beta may regulate remodeling of the extracellular matrix in calcific AS. (C) 2003 Elsevier Ireland Ltd. All rights reserved.