Abstract 5865: High-density Lipoproteins (HDL) Are Present In Stenotic Aortic Valves And May Protect Them Against Calcification

Abstract

Purpose: The pathogenesis of aortic valve stenosis (AS) is characterized by accumulation of low-density lipoprotein (LDL) cholesterol and inflammatory cells in aortic valves, as well as by marked calcification and bone formation in the affected leaflets. Hitherto, the factors which inhibit aortic valve calcification have remained obscure. We aimed to determine, whether HDL cholesterol particles enter aortic valve leaflets and whether HDL could protect the valves from cholesterol accumulation and calcification. Methods: Stenotic aortic valves were obtained from 10 AS patients undergoing valve replacement surgery. Non-stenotic control valves (n=10) were collected from cardiac transplantations. The amount and localization of HDL/apolipoprotein (apo) A-I, apoB, apoE, and osteoprotegerin (OPG) were analyzed by immunohistochemistry and computer-assisted morphometry. Myofibroblasts were isolated from aortic valves and their secretion of calcific mediators in response to HDL-stimulation was studied by real-time PCR and ELISA. Results: Accumulation of HDL/apoA-I was detected in both control and stenotic aortic valves. HDL was detected particularly around calcific deposits in the stenotic valves, in which it was colocalized with apoB and apoE, as well as with OPG. Stimulation of cultured aortic valve myofibroblasts with HDL or apoA-I significantly increased secretion of OPG by these cells (p>0.001), whereas the secretion of RANKL, which counteracts the effects of OPG, remained unchanged. Conclusions: HDL is present locally in human stenotic aortic valves and induces secretion of OPG in valvular cells in vitro. Since OPG is known to inhibit aortic valve calcification, this mechanism may provide HDL a protective role in AS.