In heart failure, activation of the transforming growth factor (TGF)-β superfamily mediates both adaptive and maladaptive cellular responses, associated with inflammation, compensatory cardiomyocyte hypertrophy and dysfunction, and fibrosis. Downstream from TGF-β signaling are two types of Smad proteins that are stimulated to act in opposite ways: Receptor-activated Smads (R-Smads) are the intracellular effectors of TGF-b signaling, whereas the Inhibitory Smads (I-Smads) restrain R-Smad responses. Regulating the expression and activity of Smad proteins could be a helpful strategy for treating heart failure.

The National Heart, Lung, and Blood Institute has awarded Nikolaos Frangogiannis, M.D., a four-year, $ 2.1 million grant to examine the role of two I-Smads, Smad6 and Smad7, in remodeling, dysfunction and fibrosis of the pressure-overloaded failing heart. Dr. Frangogiannis and his colleagues will use a mouse model to examine the mechanisms of action of the two I-Smads in cardiomyocytes, fibroblasts and immune cells, as well as their molecular targets.

Dr. Frangogiannis is professor of medicine and microbiology & immunology and the Edmond J. Safra/Republic National Bank of New York Chair in cardiovascular medicine at Einstein. (1R01HL149407-01A1)