期刊
ATHEROSCLEROSIS
卷 219, 期 2, 页码 538-544出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2011.08.027
关键词
Aortic valve stenosis; HDL; ApoA-I; OPG; TNF-alpha
资金
- Finnish Foundation for Cardiovascular Research, Helsinki, Finland
- Finnish Medical Foundation
- Helsinki University Central Hospital
- Sigrid Juselius Foundation
- Research Council for Health, Academy of Finland
Objective: To determine whether differences exist in valvular high density lipoprotein (HDL) content between non-stenotic and stenotic aortic valves, and whether HDL could retard valvular calcification locally. Methods: Stenotic aortic valves were obtained from valve replacement surgery and non-stenotic control valves from cardiac transplantations or at autopsy. The valvular localization and concentration of apolipoproteinA-I (apoA-I) were analyzed by immunohistochemistry and ELISA. The effects of HDL on the secretion of calcifying mediators and proinflammatory cytokines by cultured aortic valve myofibroblasts were assessed by ELISA and real-time PCR. Results: The concentration of apoA-I was higher in control than in stenotic valves (p < 0.05). ApoA-I surrounded the calcific deposits in stenotic valves, co-localizing with apoB, apoE, and osteoprotegerin (OPG). Incubation of cultured valve myofibroblasts with HDL increased their secretion of OPG (p < 0.001). Furthermore, incubation of myofibroblasts with HDL led to decreased mRNA expression of tumor necrosis factor alpha (TNf-alpha.) (p < 0.05). Conclusions: The amount of valvular HDL is reduced in aortic valve stenosis. HDL both induces the secretion of OPG and reduces the expression of TNF-alpha in vitro. Since OPG is known to inhibit and TNF-alpha to promote aortic valve calcification, HDL may have an anti-calcifying effect in human aortic valves. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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