Hippo-Yap signaling in cardiac and fibrotic remodeling

Cardiac injury initiates a tissue remodeling process in which aberrant fibrosis plays a significant part, contributing to impaired contractility of the myocardium and the progression to heart failure. Fibrotic remodeling is characterized by the activation, proliferation, and differentiation of quiescent fibroblasts to myofibroblasts, and the resulting effects on the extracellular matrix and inflammatory milieu. Molecular mechanisms underlying fibroblast fate decisions and subsequent cardiac fibrosis are complex and remain incompletely understood. Emerging evidence has implicated the Hippo-Yap signaling pathway, originally discovered as a fundamental regulator of organ size, as an important mechanism that modulates fibroblast activity and adverse remodeling in the heart, while also exerting distinct cell type-specific functions that dictate opposing outcomes on heart failure. This brief review will focus on Hippo-Yap signaling in cardiomyocytes, cardiac fibroblasts, and other non-myocytes, and present mechanisms by which it may influence the course of cardiac fibrosis and dysfunction.