RBM20, a Therapeutic Target to Alleviate Myocardial Stiffness Titin Isoforms Switching in HFpEF

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2022 Jul 5

PMID 35783855

Authors

Na Li

Weijian Hang

Hongyang Shu

Ning Zhou

Affiliations

Soon will be listed here.

Abstract

Increased myocardial stiffness is critically involved in heart diseases with impaired cardiac compliance, especially heart failure with preserved ejection fraction (HFpEF). Myocardial stiffness mainly derives from cardiomyocyte- and extracellular matrix (ECM)-derived passive stiffness. Titin, a major component of sarcomeres, participates in myocardial passive stiffness and stress-sensitive signaling. The ratio of two titin isoforms, N2BA to N2B, was validated to influence diastolic dysfunction several pathways. RNA binding motif protein 20 (RBM20) is a well-studied splicing factor of titin, functional deficiency of RBM20 in mice profile improved cardiac compliance and function, which indicated that RBM20 functions as a potential therapeutic target for mitigating myocardial stiffness by modulating titin isoforms. This minor review summarized how RBM20 and other splicing factors modify the titin isoforms ratio, therefore providing a promising target for improving the myocardial compliance of HFpEF.

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