期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 176, 期 6, 页码 2638-2645出版社
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2010.090541
关键词
-
类别
资金
- Canadian Institute of Health Research (CIHR), Ottawa, Canada [MOP 79342]
- Quebec Heart Institute Foundation
- Reseau d'Echanges et de Tissus Biologiques
- Fonds de Recherche en Sante du Quebec, Montreal, Canada
- Sanofi-Aventis
Aortic stenosis (AS) is the most common valvular heart disease, and it is suspected that atherosclerotic mechanisms are involved in the development of this disorder. Therefore, the retention of lipids within the aortic valve may play a role in the pathobiology of AS. In this study, a gene expression microarray experiment was conducted on human aortic valves with and without AS. The expression levels of transcripts encoding proteoglycans and enzymes involved in lipid retention were compared between the two groups. The microarray results were subsequently replicated in a cohort of 87 AS valves and 36 control valves. In addition, the interaction between proteoglycan and lipid-modifying enzyme was documented in isolated valve interstitial cells (VICs). The microarray results indicated that only biglycan (BGN) and phospholipid transfer protein (PLTP) were overexpressed in the AS valves. These results were then confirmed by quantitative PCR. The immunohistochemical analysis revealed a colocalization of BGN, PLTP, and Toll-like receptor-2 (TLR 2) in AS valves. In vitro, we showed that BGN induces the production of PLTP in VICs via the stimulation of TLR 2. Thus, increased accumulation of BGN in AS valves contributes to the production of PLTP via TLR 2. These results suggest that intricate links between valve matrix proteins, inflammation, and lipid retention are involved in the pathobiology of AS. (Am J Pathol 2010, 176:2638-2645; DOI: 10.2353/ajpath.2010.090541)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据