High-density lipoproteins (HDL) are present in stenotic aortic valves and may interfere with the mechanisms of valvular calcification

Abstract

ObjectiveTo 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. MethodsStenotic 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. ResultsThe 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-α) (p<0.05). ConclusionsThe amount of valvular HDL is reduced in aortic valve stenosis. HDL both induces the secretion of OPG and reduces the expression of TNF-αin vitro. Since OPG is known to inhibit and TNF-α to promote aortic valve calcification, HDL may have an anti-calcifying effect in human aortic valves.