Role of c‐myc in coronary vascular development and pathology

Abstract

The formation and patterning of the coronary vasculature is critical to development and pathology in the heart. During cardiac pathology and physiological growth, coordinated interactions between growth of the organ and formation of the vascular bed are present. Studies from our lab have found that c‐myc is a main regulator of the angiogenic network. Despite the importance of c‐myc in the regulation of the angiogenic cascade, little has been done to explore the role of c‐myc in the formation of the coronary vasculature. In this study we utilized c‐myc+/− mice to examine the effects of diminished c‐Myc on the formation of the vascular bed, vascular patterning, intercapillary space and cardiac function. We observed that c‐myc+/− hearts had decreased cardiac output, diminished vessel bed formation and increased innercapillary space. However, an increase in fractal values suggests an increase in vessel patterning. To recover the effects of c‐myc happloinsufficiencies we crossed c‐myc+/− to the APCmin/+ mouse model, a model in which c‐Myc is increased via β‐catenin stabilization, to make compound APCMIN/+ c‐myc+/− mice. These mice were observed to have recovered the cardiac deficiencies and vessel bed attenuation observed in the c‐myc+/− mouse. However these vessel beds were found to more tortuous and leaky. Together these data highlight the importance of c‐Myc levels in cardiac function and vascular formation.