Selective deletion of TRPM4 channels in mouse cardiomyocytes resulted in an approximately 50% reduction in left ventricular hypertrophy induced by transverse aortic constriction.
Does selective deletion of TRPM4 channels reduce pressure overload-induced left ventricular hypertrophy in mice?
TRPM4 channels are a key component of the mechanosensory signaling pathway inducing left ventricular hypertrophy, representing a potential novel therapeutic target.
Pathological left ventricular hypertrophy (LVH) occurs in response to pressure overload and remains the single most important clinical predictor of cardiac mortality. The molecular pathways in the induction of pressure overload LVH are potential targets for therapeutic intervention. Current treatments aim to remove the pressure overload stimulus for LVH, but do not completely reverse adverse cardiac remodelling. Although numerous molecular signalling steps in the induction of LVH have been identified, the initial step by which mechanical stretch associated with cardiac pressure overload is converted into a chemical signal that initiates hypertrophic signalling remains unresolved. In this study, we show that selective deletion of transient receptor potential melastatin 4 (TRPM4) channels in mouse cardiomyocytes results in an approximately 50% reduction in the LVH induced by transverse aortic constriction. Our results suggest that TRPM4 channel is an important component of the mechanosensory signalling pathway that induces LVH in response to pressure overload and represents a potential novel therapeutic target for the prevention of pathological LVH.
Guo et al. (Wed,) conducted a other in Pathological left ventricular hypertrophy. Selective deletion of TRPM4 channels vs. Control mice was evaluated on Left ventricular hypertrophy induced by transverse aortic constriction. Selective deletion of TRPM4 channels in mouse cardiomyocytes resulted in an approximately 50% reduction in left ventricular hypertrophy induced by transverse aortic constriction.