The Role of Vascular Smooth Muscle Specific Growth Differentiation Factor (GDF 11) in Coronary Collateral Growth Induced by Repetitive Ischemia

Coronary heart diseases (CHD) are the leading cause of mortality and morbidity in the United States. When the CHD patient has well-developed coronary collateral circulation, the outcome of cardiac events is much better. The importance of coronary collaterals, a natural bypass for CHD, is undisputable, but the process and underlying mechanism of coronary collateral growth (CCG) are unclear. We developed a mouse model of CCG by repetitive ischemia (RI) in adulthood. In this study, we investigate the role of smooth muscle-specific growth differentiation factor 11 (GDF11) in CCG. GDF11 has been reported to be related to age-related heart hypertrophy, but its role in CCG is unknown. Global deletion of Gdf11 is perinatal lethal. We first use non-inducible smooth muscle cells (SMC)-specific cre (SM-22-cre) crossed with Gdf11 f/f to generate the SMC-specific Gdf11 knockouts (Gdf11 DSMC ), which are viable. To exclude the effect of embryonic development, we use inducible VSMCs-specific cre (Itag8-Cre-ER) to generate inducible SMC-specific Gdf11 knockouts (Gdf11 i DSMC ). We also use lineage tracing mice (Td-tomato- Itag8-Cre-ER) to study the role of SMC in CCG. We use 3D imaging (micro-CT and light sheet) to analyze whole mouse heart coronary vasculature, contrast echo to measure the coronary blood flow, and single cell-RNA sequencing (scRNA-Seq) to analyze the molecular signaling of CCG at different time points during the RI. We also compared the phenotype of Gdf11 DSMC and Gdf11 i DSMC at the baseline and under metabolic stress. Our preliminary data showed that increased CCG in Gdf11 DSMC mice fed on a chow diet decreased coronary vasculature in Gdf11 DSMC mice fed on an HFHS diet, suggesting the different role of SMC-GDF 11 under metabolic stress. sc-RNA showed the dynamic kinetics of non-cardiomyocytes, and EC expression profiling varied in response to RI throughout CCG. Ongoing studies aim at understanding the underlying mechanism. 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.