IntroductionAortic valve stenosis (AVS) is the most common valvular disease and the only treatment currently is valve replacement. Our group showed that a mimetic peptide of apolipoprotein A-I (apoA-I), the major protein of HDL, exerts benefits on AVS in mice and rabbits. However, we have shown that AVS patients do not appear to possess dysfunctional HDL. AVS involves multiple events including lipoprotein deposition, inflammation and oxidation. The scavenger receptor class B type I (SR-BI) is a major apoA-I/HDL receptor expressed in human aortic valves. Signaling mediated by apoA-I binding to SR-BI exerts anti-inflammatory and vasorelaxant benefits. Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) contribute to endothelial cell dysfunction and atherosclerosis. HDL can be altered during inflammation and can increase LOX-1 expression. We hypothesize that changes in apoA-I/HDL target receptor expression may lead to decreased benefits of endogenous HDL in valves from AVS patients. The aims of this study were to investigate the serum levels of soluble SR-B1 and sLOX-1 in patients with AVS and analyse their expression in valve specimens.MethodsSerum sLOX-1 and SR-BI levels were measured in patients with AVS but no coronary artery disease (CAD) (n=16), patients with both AVS and CAD (n=16), and in control subjects (n=12) using an ELISA method. Immunochemistry, immunofluorescence and qPCR analysis were performed on human calcified aortic valves collected from patients who underwent valve replacement and human normal aortic valves from patients who underwent heart transplant.ResultsSerum sLOX-1 level is significantly higher in AVS patients compared with control subjects (p<0.05) and appears to be even higher in patients with both AVS and CAD (ns). Immunohistochemical stainings against LOX-1 indicates a strong signal in calcified AVS compared to normal valves. Serum SR-BI level was significantly decreased in AVS patients compared with control subjects (p<0.05), although we did not observe a difference in terms of mRNA expression for SR-BI in the valves.ConclusionSerum SR-BI and LOX-1 are inversely modulated in patients with AVS. Analyses of additional patients for both serum levels and complementary immunohistochemical analyses are being performed. These findings suggest that alterations of the apoA-I/HDL target receptors SR-B1 and LOX-1 may modulate the effects of HDL in AVS. IntroductionAortic valve stenosis (AVS) is the most common valvular disease and the only treatment currently is valve replacement. Our group showed that a mimetic peptide of apolipoprotein A-I (apoA-I), the major protein of HDL, exerts benefits on AVS in mice and rabbits. However, we have shown that AVS patients do not appear to possess dysfunctional HDL. AVS involves multiple events including lipoprotein deposition, inflammation and oxidation. The scavenger receptor class B type I (SR-BI) is a major apoA-I/HDL receptor expressed in human aortic valves. Signaling mediated by apoA-I binding to SR-BI exerts anti-inflammatory and vasorelaxant benefits. Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) contribute to endothelial cell dysfunction and atherosclerosis. HDL can be altered during inflammation and can increase LOX-1 expression. We hypothesize that changes in apoA-I/HDL target receptor expression may lead to decreased benefits of endogenous HDL in valves from AVS patients. The aims of this study were to investigate the serum levels of soluble SR-B1 and sLOX-1 in patients with AVS and analyse their expression in valve specimens. Aortic valve stenosis (AVS) is the most common valvular disease and the only treatment currently is valve replacement. Our group showed that a mimetic peptide of apolipoprotein A-I (apoA-I), the major protein of HDL, exerts benefits on AVS in mice and rabbits. However, we have shown that AVS patients do not appear to possess dysfunctional HDL. AVS involves multiple events including lipoprotein deposition, inflammation and oxidation. The scavenger receptor class B type I (SR-BI) is a major apoA-I/HDL receptor expressed in human aortic valves. Signaling mediated by apoA-I binding to SR-BI exerts anti-inflammatory and vasorelaxant benefits. Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) contribute to endothelial cell dysfunction and atherosclerosis. HDL can be altered during inflammation and can increase LOX-1 expression. We hypothesize that changes in apoA-I/HDL target receptor expression may lead to decreased benefits of endogenous HDL in valves from AVS patients. The aims of this study were to investigate the serum levels of soluble SR-B1 and sLOX-1 in patients with AVS and analyse their expression in valve specimens. MethodsSerum sLOX-1 and SR-BI levels were measured in patients with AVS but no coronary artery disease (CAD) (n=16), patients with both AVS and CAD (n=16), and in control subjects (n=12) using an ELISA method. Immunochemistry, immunofluorescence and qPCR analysis were performed on human calcified aortic valves collected from patients who underwent valve replacement and human normal aortic valves from patients who underwent heart transplant. Serum sLOX-1 and SR-BI levels were measured in patients with AVS but no coronary artery disease (CAD) (n=16), patients with both AVS and CAD (n=16), and in control subjects (n=12) using an ELISA method. Immunochemistry, immunofluorescence and qPCR analysis were performed on human calcified aortic valves collected from patients who underwent valve replacement and human normal aortic valves from patients who underwent heart transplant. ResultsSerum sLOX-1 level is significantly higher in AVS patients compared with control subjects (p<0.05) and appears to be even higher in patients with both AVS and CAD (ns). Immunohistochemical stainings against LOX-1 indicates a strong signal in calcified AVS compared to normal valves. Serum SR-BI level was significantly decreased in AVS patients compared with control subjects (p<0.05), although we did not observe a difference in terms of mRNA expression for SR-BI in the valves. Serum sLOX-1 level is significantly higher in AVS patients compared with control subjects (p<0.05) and appears to be even higher in patients with both AVS and CAD (ns). Immunohistochemical stainings against LOX-1 indicates a strong signal in calcified AVS compared to normal valves. Serum SR-BI level was significantly decreased in AVS patients compared with control subjects (p<0.05), although we did not observe a difference in terms of mRNA expression for SR-BI in the valves. ConclusionSerum SR-BI and LOX-1 are inversely modulated in patients with AVS. Analyses of additional patients for both serum levels and complementary immunohistochemical analyses are being performed. These findings suggest that alterations of the apoA-I/HDL target receptors SR-B1 and LOX-1 may modulate the effects of HDL in AVS. Serum SR-BI and LOX-1 are inversely modulated in patients with AVS. Analyses of additional patients for both serum levels and complementary immunohistochemical analyses are being performed. These findings suggest that alterations of the apoA-I/HDL target receptors SR-B1 and LOX-1 may modulate the effects of HDL in AVS.