Role of angiopoietin-1 in cardiac development

Abstract

Cardiac chamber morphogenesis is substantially influenced by the interaction between the myocardium and endocardium. Angiopoietin-1 (Angpt1), a crucial factor for cardiovascular development, is expressed in the myocardium and known to be indispensable for the cardiac chamber morphogenesis, but the exact underlying molecular mechanism remains uncovered. Angpt1 is selectively expressed in atrial and trabecular myocardium of developing heart. Global or cardiac-specific deletion of Angpt1 lead to myocardial thickening and excessive deposition of cardiac jelly, which disturbs segmentation and expansion of atrial chambers as well as trabeculation in ventricles. Angpt1/Tie2 signaling positively regulates the expression of ADAMTS proteases in endocardium, thereby promoting degradation of versican protein in cardiac jelly. Taken together, this study reveals a novel function of myocardial Angpt1 in cardiac chamber morphogenesis and suggest a possible implication of cardiac jelly in the pathogenesis of congenital cardiac defects.