Resolution of inflammation in healing myocardial infarcts

NARRATIVE Transforming Growth Factor (TGF)- superfamily members play a critical role in repair, remodeling and fibrosis of the infarcted heart, signaling through intracellular effectors, the Smads and through non-Smad pathways. The current proposal will investigate cell- specific actions of Smad1 cascades in the infarcted heart. In vivo experiments using cell- specific knockout mice, in vitro loss- and gain-of-function studies and single cell RNAseq experiments will be performed to study Smad1-mediated actions on fibroblasts, macrophages, cardiomyocytes and pericytes, to dissect the molecular mechanisms responsible for Smad1 effects, and to explore the role of TGF- signaling responses in mediating subset-specific functions of immune and reparative cells.