Key result
Cardiomyocyte TRPV4 deletion attenuates isoproterenol-induced cardiac hypertrophy and preserves function via PKG1 signaling.
Why the study?
The specific contribution of cardiomyocyte TRPV4 channels to pathological cardiac remodeling remained unknown.
Does cardiomyocyte-specific TRPV4 deletion prevent isoproterenol-induced cardiac hypertrophy and dysfunction in mice?
Does cardiomyocyte-specific TRPV4 deletion prevent isoproterenol-induced cardiac hypertrophy and dysfunction in mice?
Cardiomyocyte-specific TRPV4 deletion protects against isoproterenol-induced cardiac hypertrophy and dysfunction by modulating PKG1 signaling, identifying a potential therapeutic target for heart failure.
Answers are grounded in this paper and cite their sources.
Cardiomyocyte TRPV4 deletion prevents isoproterenol-induced hypertrophy; extends prior global and endothelial protection to muscle-specific mechanisms.
Left ventricular hypertrophy (LVH) represents an adaptive response to volume stress or pressure overload but can progress to contractile dysfunction and heart failure. Previously, we demonstrated that global or endothelial-specific deletion of transient receptor potential vanilloid 4 (TRPV4) channels protects against adverse cardiac remodeling following myocardial infarction (MI) or pressure overload (TAC) by inhibiting fibroblast differentiation or enhancing coronary angiogenesis, respectively. However, the specific contribution of cardiomyocyte TRPV4 to pathological remodeling remains unknown. To address this, we generated cardiomyocyte-specific TRPV4 knockout (TRPV4MKO) mice and subjected them to isoproterenol (ISO; 40 mg/kg/day)-induced cardiac hypertrophy for 14 days. ISO treatment induced significant hypertrophy in TRPV4lox/lox control mice but not in TRPV4MKO mice. In contrast, ISO provoked comparable interstitial fibrosis in both genotypes. Echocardiographic assessment revealed that cardiac function, as indicated by ejection fraction and fractional shortening, declined in TRPV4lox/lox mice but was preserved in TRPV4MKO mice. Single-nucleus RNA sequencing analysis showed marked downregulation of protein kinase G1 (PKG1) expression in hearts from patients with hypertrophic cardiomyopathy compared with healthy controls. Mechanistically, TRPV4 inhibition increased PKG1 expression and attenuated ISO-induced hypertrophy in AC16 human cardiomyocytes. Conversely, pharmacological inhibition of PKG1 with KT5823 exacerbated hypertrophic responses to ISO. Taken together, these findings suggest that cardiomyocyte-specific deletion of TRPV4 mitigates adverse cardiac remodeling by modulating PKG1 signaling, identifying the TRPV4–PKG1 axis as a potential therapeutic target for heart failure. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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Katari et al. (2026) studied Cardiac hypertrophy. Cardiomyocyte-specific TRPV4 deletion vs. TRPV4lox/lox control mice was evaluated on Cardiac hypertrophy and cardiac function (ejection fraction and fractional shortening). Cardiomyocyte-specific deletion of TRPV4 attenuated cardiac hypertrophy induced by 14 days of isoproterenol and preserved cardiac function via PKG1 signaling.
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