NAKAOKA Yoshikazu ≪Cardiovascular Medicine≫ “Gab family proteins are essential for postnatal maintenance of cardiac function via neuregulin-1/ErbB signaling.”
Publish Journal of Clinical Investigation; 117, 1771-1781, 2007
I examined the role of Gab family proteins in the heart by creating cardiomyocyte-specific Gab1/Gab2-double knockout (DKO) mice. DKO mice were viable, but exhibited marked ventricular dilatation and reduced contractility with aging. NRG-1β induced activation of both ERK and AKT in the hearts of control mice, but not in those of DKO mice. In addition, endocardial fibroelatsosis and abnormally dilated vessels were observed in the ventricles of DKO mice. NRG-1β upregulated expression of an endothelium-stabilizing factor, angiopoeitin-1, in the hearts of control mice, but not in those of DKO mice, possibly accounting for the pathological abnormalities in the DKO hearts. Collectively, Gab1 and Gab2 are essential for both maintenance of myocardial function and stabilization of cardiac capillary/endocardial endothelium through transmitting NRG-1β/ErbB signaling in the postnatal heart.