The Regulatory Role of Endothelial CXCR4 in Cardiac Function

CXCR-4 is an alpha-chemokine receptor specific for stromal-derived factor-1 (SDF-1, also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. CXCR4 and CXCL12 signaling pathways are important for stem cell homing in myocardial ischemia and cardiovascular regeneration. Endothelial cells are a key player in maintaining vascular homeostasis. The global CXCR knockout mice are lethal, suggesting the essential role of the CXCL12 and CXCR4 signaling pathways in cardiovascular diseases. However, the role of CXCR4 in endothelial cells in vascular function and ischemic heart diseases is unknown. In this study, we use genetically modified mice (CXCR4 endothelial cell-specific knockout) to study the role of CXCR4 in endothelial cells in cardiovascular diseases such as diabetes. We have two groups of mice, the Cxcr4 floxed mice (Control mice), Cxcr4 floxed-Cadh5-cre mice (CXCR4 endothelial cell-specific knockout). Both groups of mice were fed on a chow or high fat and high sugar (HFHS) diet for six months. We performed echocardiography at different time points. The mice were under anesthesia with 2-3% isoflurane, and cardiac function was measured with B or M-mode and tissue Doppler. Then, the files were exported to a computer installed with the Vevo software. 3-5 measurements from different frames of images of each mouse for cardiac function systolic and diastolic cardiac function. Our preliminary data showed that 1) mice fed with a fat and high-sugar diet for six months developed diabetes with high plasma glucose levels and insulin resistance. 2) The cardiac function of mice on the HFHS diet was worse than that of the mice on the chow diet. 3) Knockout CXCR4 in endothelial cells caused cardiovascular dysfunction. It suggested that CXCR4/CXCL12 signaling pathway could be a potential target for developing a treatment for ischemic heart diseases. AHA This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.