The Hippo Signaling Pathway as a Drug Target in Familial Dilated Cardiomyopathy

Abstract

Review The Hippo Signaling Pathway as a Drug Target in Familial Dilated Cardiomyopathy Paulina Langa 1, Beata M. Wolska1,2, R. John Solaro1,* 1 Department of Physiology and Biophysics and the Center for Cardiovascular Research,University of Illinois at Chicago, Chicago, IL,USA. 2 Department of Medicine, Division of Cardiology, College of Medicine, University of Illinois at Chicago, Chicago, IL,USA. * Correspondence: solarorj@uic.edu, Tel.: +1 (312)-420-0241, +1(312)-996-8546, Fax: +1 (312) 996-1414     Received: 1 November 2022 Accepted: 24 November 2022 Published: 21 December 2022   Abstract: We focus here on the Hippo pathway in the hierarchical sensing and modulation of the mechanical state of the adult heart in health and disease. The Hippo pathway interrogates the micro-environment of cardiac myocytes providing surveillance of the mechanical state with engagement of signaling pathways critical to homeostasis of cardiac development, remodeling, and function and vulnerable to pathologies. Our discussion centers on Hippo signaling in the altered mechanical state instigated by variants of genes expressing mutant sarcomere proteins that trigger a progression to dilated cardiomyopathy (familial DCM). There is an unmet need for therapies in DCM. Recent progress in the discovery of small molecules that target Hippo signaling and are intended for use in cardiac disorders provides leads for modifying Hippo in DCM. As we emphasize, identifying useful targets in DCM requires in depth understanding of cell specific Hippo signaling in the cardiac micro-environment.