Genetic and epigenetic regulation of coronary vasculature by 3D imaging

Coronary artery disease (CAD) is a leading cause of death worldwide despite many surgical and pharmacological advances. Many efforts have been invested in preventing atherosclerosis and in cardiac regeneration after myocardial ischemia injury; however, the role of the structure and function of coronary vasculature in CAD is not fully understood. The abnormal structural and functional changes of coronary vasculature adversely affect coronary blood flow and myocardial perfusion, which leads to myocardial ischemia, especially with the prevalence of metabolic syndrome. This study focuses on a unique niche to investigate the relationship between coronary vasculature and cardiac function under physiological conditions, pathological conditions (e.g. diabetes), and with stimulation of repetitive ischemia (RI). We used transgenic mice fed a regular (chow) diet and a high-fat, high-sugar (HFHS) diet to study the effect of metabolic stress on the coronary vasculature. For 3D imaging of coronary vasculature trees, the mice were perfused with microfil and the hearts were imaged with brightfield scope and scanned with micro-CT. The 3D structure of the coronary vasculature was analyzed using Avizo and Analyze software. To study the effect of RI, the mice underwent an established RI protocol, as we published. We also use light sheet scope to image the coronary vasculature of lineage-tracing animals. Preliminary results show that 1) native wild-type mouse hearts have a well-developed coronary vasculature with three major branches: left coronary arteries, right coronary arteries and septum; 2) native hearts have no native coronary collaterals; 3) Structural and volumetric vasculature varies among the genes and diet; 4) The coronary vasculature is more abundant in response to RI in the wildtype mice fed on chow diet, but did not change in the diabetic animals. 5) The vascular endothelial cells and smooth muscle cells contribute differently in response to RI. This study highlights the adaptive response of coronary vasculature to metabolic stress, genetic regulation, and RI. The findings provide insights into how coronary artery structure affects cardiac function, leading to new therapeutic strategies for CAD and IHD. AHA and NIH 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.