Antagonizing YAP to reduce cardiac fibrosis

The last chapter in the mechanistic understanding of fibrotic process in the ischemic heart has been written by the group of M. Singh with the selective inhibition of YAP/TAZ activation in cardiac fibroblasts in mice with myocardial infarction. Using a genetic approach with the aim at selectively target YAP function in fibroblasts, the Authors show that YAP transcriptional signalling abrogation in vivo not only attenuated the post infarct fibrosis and the maladaptive ventricular remodelling, but also interfered with the cross talk between cardiac fibroblasts and cells of the innate immunity response by reducing inflammatory cytokines secretion and macrophage polarization. In the study, YAP signalling was found to cooperate with TGF-beta and Wnt in controlling cardiac inflammation and fibrosis. These data provide a new demonstration of the role of the Hippo transcriptional pathway in cardiac fibrosis and suggest novel possibilities for reducing the consequence of ischemic myocardial remodelling in patients with acute MI or coronary artery disease.