Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart

The post-natal heart adapts to stress and overload through hypertrophic growth, a process that may be pathologic or beneficial （physiologic hypertrophy）. Physiologic hypertrophy improves cardiac performance in both healthy and diseased individuals, yet the mechanisms that propagate this f~vorable adaptation remain poorly defined. We identify the cytokine cardiotrophin 1 （CT1） as a factor capable of recapitulating the key features of physiologic growth of the heart including transient and reversible hypertrophy of the myocardium, and stimulation of cardiomyocyte-derived angiogenic signals leading to increased vascularity. The capacity of CT1 to induce physiologic hypertrophy originates from a CK2-mediated restraining of caspase activation, preventing the transition to unrestrained pathologic growth. Exogenous CT1 protein delivery attenuated pathology and restored contractile function in a severe model of right heart failure, suggesting a novel treatment option for this intractable cardiac disease.