Abstract 14024: Role of Endothelial CXCR4 on the Development of Aortic Valve Stenosis

Background. CXCL12/CXCR4 signaling is essential in cardiac development and repair, however, its contribution to the Aortic valve stenosis (AVS) remains unclear. In this study, we tested the role of endothelial CXCR4 on the development of AVS. Methods. We generated CXCR4 endothelial cell-specific knockout mice (EC CXCR4 KO) by crossing CXCR4 fl/fl mouse with Tie2-Cre mouse to study the role of endothelial cell CXCR4 in AVS. CXCR4 fl/fl mice with no Tie2-Cre gene present were used as control. Echocardiography was used to assess the aortic valve and cardiac function. Heart samples containing the aortic valve were stained using Alizarin Red for detection of calcification. Masson’s Trichrome staining was used for the detection of fibrosis. Apex samples were stained with wheat germ agglutinin to visualize ventricular hypertrophy. Results. Compared with the control group, the deletion of CXCR4 in endothelial cells led to significantly increased aortic valve peak velocity and aortic valve peak pressure gradient, and decreased aortic valve area and ejection fraction. EC CXCR4 KO mice also developed cardiac hypertrophy evidenced by increased left ventricular mass, diastolic and systolic left ventricle posterior wall (LVPW), cardiac myocyte size, and heart weight (HW) to body weight (BW) ratio. Our data also confirmed increased microcalcifications, interstitial fibrosis, and thickened valvular leaflets of the EC CXCR4 KO mice. Conclusions. We found that the deletion of CXCR4 in endothelial cells leads to aortic valve stenosis and left ventricular hypertrophy. This indicates endothelial cell CXCR4 plays a protective role against AVS, and EC CXCR4 KO mice can be used as a novel model for AVS study.