Cellular decisions in cardiac outflow tract and coronary development: An act by VEGF and NOTCH

Congenital cardiac abnormalities are, due to their relatively high frequency and severe impact on quality of life, an important focus in cardiovascular research. Recently, various human studies have revealed a high coincidence of VEGF and NOTCH polymorphisms with cardiovascular outflow tract anomalies, such as bicuspid aortic valves and Tetralogy of Fallot, next to predisposition for cardiovascular pathologies, including atherosclerosis and aortic valve calcification. This genetic association between VEGF/NOTCH mutations and congenital cardiovascular defects in humans has been supported by substantial proof from animal models, revealing interaction of both pathways in cellular processes that are crucial for cardiac development.This review focuses on the role of VEGF and NOTCH signaling and their interplay in cardiogenesis with special interest to coronary and outflow tract development. An overview of the association between congenital malformations and VEGF/NOTCH polymorphisms in humans will be discussed along with their potential mechanisms and processes as revealed by transgenic mouse models. The molecular and cellular interaction of VEGF and subsequent Notch-signaling in these processes will be highlighted.