The role of CXCR4 in vascular endothelial cells in ischemic heart diseases
| Autor: | Yang Wang, James Gadd, Molly Enrick, Blessing Ogunmiluyi, SARAH Dong, Lily Zhang, Laura Zhang, Liya Yin |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Physiology. 38 |
| ISSN: | 1548-9221 1548-9213 |
| Popis: | CXCR4 and CXCL12 signaling pathways are essential in cardiovascular development, ischemia heart diseases, and cardiovascular regeneration. Coronary collaterals are nature bypass of ischemic heart diseases. Recently reports showed that CXCR4 and CXCL12 signaling is involved in coronary collateral growth (CCG) in a mouse model of myocardial infarction. Our study showed that endothelial cell (EC) sprouting is essential to coronary collateral formation in a mouse model of CCG induced by repetitive ischemia (RI). It is unknown the role of CXCR4 in EC in CCG. In this study, we used genetically modified mice (CXCR4 EC-specific knockout) to study the role of CXCR4 in ECs in myocardial ischemia. First, we generated EC-specific CXCR4 knockout (CXCR4 flox/flox-tie-2-cre). Surprisingly we found spontaneous aortic stenosis in these EC-specific CXCR4 knockout mice. To exclude the effect of CXCR4 in ECs during embryonic development, we generated an inducible CXCR4 EC-specific knockout (CXCR4 flox/flox-VE-cadherin-cre). Our preliminary data showed no aortic stenosis in these mice after being induced by tamoxifen at six weeks old, suggesting that CXCR4 signaling in EC affects cardiovascular development. We compared the phenotypes of two mouse lines of CXCR4 endothelial knockouts by echocardiography and histology. Furthermore, these CXCR4 EC-specific knockout mice and their littermate controls underwent myocardial infarction (MI) and RI surgery. We measured the cardiac function, vessel density, and coronary blood flow in the mice with RI. We measured the cardiac function, vessel density and infarction size, and fibrosis in the mice with MI. Our preliminary data showed that the CXCR4 and CXCL12 signaling in vascular EC is essential to cardiovascular regeneration during myocardial ischemia, suggesting that CXCR4/CXCL12 signaling pathway could be a potential target for treating ischemic heart diseases and preventing heart attack. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process. |
| Databáze: | OpenAIRE |
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