The Wnt/frizzled pathway in cardiovascular development and disease: friend or foe?

Proteins from the Wnt family have been implicated in cell-cell communication in a wide variety of developmental and physiological processes. Wnt signaling is required for different aspects of cardiac and vascular development, including myocardial specification, cardiac morphogenesis and cardiac valve formation as well as endothelial and vascular smooth muscle cell proliferation. Defective Wnt signaling can result in different cardiac and vascular abnormalities. In the adult heart and blood vessels, Wnt signaling activity is quite low under normal conditions. However, this pathway is reactivated during the pathological cardiac remodeling induced by pressure overload, in injured arteries and after myocardial infarction. Genetically modified animal models have shown that inhibition of Wnt signaling results in increased angiogenesis, better infarct healing and an attenuated hypertrophic response of the heart. This suggests that pharmacological inhibition of Wnt signaling could provide a novel therapeutic strategy to prevent excessive cardiac and vascular remodeling.