TY - JOUR TI - The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy AU - Guo, Yang AU - Yu, Ze-Yan AU - Wu, Jianxin AU - Gong, Hutao AU - Kesteven, Scott AU - Iismaa, Siiri E AU - Chan, Andrea Y AU - Holman, Sara AU - Pinto, Silvia AU - Pironet, Andy AU - Cox, Charles D AU - Graham, Robert M AU - Vennekens, Rudi AU - Feneley, Michael P AU - Martinac, Boris A2 - Emoto, Noriaki A2 - Barton, Matthias A2 - Takahashi, Ken A2 - Blanton, Robert VL - 10 PY - 2021 DA - 2021/06/30 SP - e66582 C1 - eLife 2021;10:e66582 DO - 10.7554/eLife.66582 UR - https://doi.org/10.7554/eLife.66582 AB - 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. KW - mechanosensitive channels KW - left ventricular hypertrophy KW - cardiovascular disease KW - Ca2+/calmodulin-dependent protein kinase II JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -