Language

English

Publication Date

11-1-2025

Journal

Physiology

DOI

10.1152/physiol.00003.2025

PMID

40358043

PMCID

PMC12353178

PubMedCentral® Posted Date

5-13-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Ischemic heart disease, which affects more than 200 million people worldwide, is caused by reduced blood flow to the heart and leads to widespread cardiomyocyte death. Due to the limited regenerative potential of cardiomyocytes, the lost tissue is replaced by a fibrotic scar, resulting in reduced cardiac function and progression to heart failure. Current therapeutic interventions aim to improve blood flow but cannot address the inability of cardiomyocytes to renew after injury. However, multiple studies have shown that modulating the Hippo signaling pathway to activate Yes-associated protein (YAP), a transcription coactivator, in adult murine and porcine cardiomyocytes induces robust cardiomyocyte proliferation. Here, we discuss the therapeutic potential of YAP activation in the context of cardiac renewal, with a focus on both cardiomyocyte intrinsic mechanisms and the role of the microenvironment. These findings provide important insights into cardiac regeneration and strategies for developing therapies for human patients.

Keywords

Animals, Regeneration, Humans, Hippo Signaling Pathway, Myocytes, Cardiac, Signal Transduction, Protein Serine-Threonine Kinases, Heart, YAP-Signaling Proteins, Cell Proliferation

Published Open-Access

yes

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