Key result
Hippo pathway inhibitors show preclinical promise for treating familial DCM.
Why the study?
There is an unmet need for therapies in dilated cardiomyopathy.
This review highlights the Hippo-Yap mechano-sensing pathway as a promising therapeutic target for familial dilated cardiomyopathy while emphasizing the necessity of understanding cell-type-specific signaling within the cardiac microenvironment before clinical translation.
Answers are grounded in this paper and cite their sources.
Hippo modulators merit further preclinical testing in familial dilated cardiomyopathy; cell-specific mechanisms must be resolved before translation.
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.
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Langa et al. (2022) conducted a review in Familial dilated cardiomyopathy (DCM). Small molecules targeting the Hippo signaling pathway (e.g., TRULI1, XMU-MP-1) was evaluated. Small molecules targeting the Hippo signaling pathway, such as TRULI1 and XMU-MP-1, offer promising preclinical leads for treating familial dilated cardiomyopathy, though cell-specific signaling must be further elucidated.
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