Role of endothelial CXCR4 in the development of aortic valve stenosis

Title

Role of endothelial CXCR4 in the development of aortic valve stenosis

Creator

Anna Winnicki
James Gadd
Vahagn Ohanyan
Gilbert Hernandez
Yang Wang
Molly Enrick
Hannah McKillen
Matthew Kiedrowski
Dipan Kundu
Karlina Kegecik
Marc Penn
William M Chilian
Liya Yin
Feng Dong

Date

2022

Description

Background: CXCL12/CXCR4 signaling is essential in cardiac development and repair, however, its contribution to aortic valve stenosis (AVS) remains unclear. In this study, we tested the role of endothelial CXCR4 on the development of AVS.

Materials and methods: We generated CXCR4 endothelial cell-specific knockout mice (EC CXCR4 KO) by crossing CXCR4fl/fl mice with Tie2-Cre mice to study the role of endothelial cell CXCR4 in AVS. CXCR4fl/fl mice were used as controls. 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. The apex of the heart samples was stained with wheat germ agglutinin (WGA) 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, with decreased aortic valve area and ejection fraction. EC CXCR4 KO mice also developed cardiac hypertrophy as evidenced by increased diastolic and systolic left ventricle posterior wall thickness (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.

Conclusion: The data collected throughout this study suggest the deletion of CXCR4 in endothelial cells is linked to the development of aortic valve stenosis and left ventricular hypertrophy. The statistically significant parameters measured indicate that endothelial cell CXCR4 plays an important role in aortic valve development and function. We have compiled compelling evidence that EC CXCR4 KO mice can be used as a novel model for AVS.

Source

Front Cardiovasc Med
. 2022 Sep 6;9:971321. doi: 10.3389/fcvm.2022.971321. eCollection 2022.

Language

English

Citation

Anna Winnicki et al., “Role of endothelial CXCR4 in the development of aortic valve stenosis,” NEOMED Bibliography Database, accessed March 28, 2024, https://neomed.omeka.net/items/show/12087.