Blockade of Fibroblast YAP Attenuates Cardiac Fibrosis and Dysfunction Through MRTF-A Inhibition

Overview

Journal JACC Basic Transl Sci

Date 2020 Oct 5

PMID 33015415

Citations 65

Authors

Jamie Francisco

Yu Zhang

Jae Im Jeong

Wataru Mizushima

Shohei Ikeda

Andreas Ivessa

Shinichi Oka

Peiyong Zhai

Michelle D Tallquist

Dominic P Del Re

Affiliations

Soon will be listed here.

Abstract

Fibrotic remodeling of the heart in response to injury contributes to heart failure, yet therapies to treat fibrosis remain elusive. Yes-associated protein (YAP) is activated in cardiac fibroblasts by myocardial infarction, and genetic inhibition of fibroblast YAP attenuates myocardial infarction-induced cardiac dysfunction and fibrosis. YAP promotes myofibroblast differentiation and associated extracellular matrix gene expression through engagement of TEA domain transcription factor 1 and subsequent de novo expression of myocardin-related transcription factor A. Thus, fibroblast YAP is a promising therapeutic target to prevent fibrotic remodeling and heart failure.

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