Language

English

Publication Date

12-1-2025

Journal

Nature Cardiovascular Research

DOI

10.1038/s44161-025-00744-9

PMID

41233538

PMCID

PMC13138845

PubMedCentral® Posted Date

5-5-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Myocardial infarction (MI) affects millions of people worldwide, causing irreversible injury to the heart and impairing cardiac function1. In both mouse and pig MI models, activating YAP in cardiomyocytes (CMs) stimulates regenerative repair2,3. Here we developed an adeno-associated virus 9 (AAV9)-based therapy, termed CM-YAPon, which enables transient expression of an active YAP variant (YAP5SA) in CMs following exposure to the small molecule LMI070. A single LMI070 dose in mice triggers YAP5SA expression, CM cell cycle re-entry, and reprogramming of the cardiac microenvironment. YAP5SA induction after MI rapidly improves cardiac function while pre-MI induction confers cardioprotection and reduces cell death across multiple cardiac cell types. These findings reveal the therapeutic potential of reversible gene activation for ischemic heart disease.

Keywords

Animals, Myocardial Infarction, Myocytes, Cardiac, Disease Models, Animal, YAP-Signaling Proteins, Dependovirus, Genetic Therapy, Adaptor Proteins, Signal Transducing, Mice, Inbred C57BL, Mice, Humans, Male, Cell Cycle Proteins, Ventricular Function, Left

Published Open-Access

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