0269: Vascular remodeling of the endocardium following cardiac infarction occured by arteriogenesis and angiogenesis

Abstract

Coronary vasculature is required to maintain cardiomyocyte survival, via delivery of oxygen and nutrients, and consequently myocardial architecture and cardiac function. Ischemic heart disease following myocardial infarction causes irreversible cell loss and scaring and is a major cause of morbidity and mortality. Revascularization of injured, ischemic and regenerating organs is essential to restore organ function and requires the formation of new vessels by the mechanisms of vasculogenesis, angiogenesis or arteriogenesis. With the objective of studying vascular remodeling during myocardial infarction (MI), we have performed permanent left coronary ligation on Connexin40-GFP ( Cx40 GFP/ + ) mice. Cx40 encodes a gap junction protein and is expressed in endothelial cells of large vessels. In the heart, Cx40-GFP expression is detected in coronary arteries but not in veins, capillaries or endocardium. After two weeks of ligation, MI was detected in left ventricle by echocardiography and anatomical examination of these hearts revealed the presence of an extensive network of GFP-positive vasculature within the infarct area. These vessels follow a tortuous route in the remaining ventricular wall and some communicate with the left ventricular lumen forming a crater covered with GFP and VEGF-R2 positive endothelial cells at the endocardial surface. To determine whether these vessels result from neo-vascularization or coronary artery remodeling, we carried out genetic lineage tracing of coronary endothelial cells using an inducible Cx40-cre allele. Our results show that GFP positive endothelial cells forming the endocardial carters are not always derived from preexisting coronary arteries, suggesting that endocardium may also contribute to the generation of new vessels during vascular remodeling in the adult heart by angiogenesis.