The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy
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 treatmen...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/66582 |
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doaj-e5eac8e184ce43e695d6df669f74745c |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Yang Guo Ze-Yan Yu Jianxin Wu Hutao Gong Scott Kesteven Siiri E Iismaa Andrea Y Chan Sara Holman Silvia Pinto Andy Pironet Charles D Cox Robert M Graham Rudi Vennekens Michael P Feneley Boris Martinac |
| spellingShingle |
Yang Guo Ze-Yan Yu Jianxin Wu Hutao Gong Scott Kesteven Siiri E Iismaa Andrea Y Chan Sara Holman Silvia Pinto Andy Pironet Charles D Cox Robert M Graham Rudi Vennekens Michael P Feneley Boris Martinac The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy eLife mechanosensitive channels left ventricular hypertrophy cardiovascular disease Ca2+/calmodulin-dependent protein kinase II |
| author_facet |
Yang Guo Ze-Yan Yu Jianxin Wu Hutao Gong Scott Kesteven Siiri E Iismaa Andrea Y Chan Sara Holman Silvia Pinto Andy Pironet Charles D Cox Robert M Graham Rudi Vennekens Michael P Feneley Boris Martinac |
| author_sort |
Yang Guo |
| title |
The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy |
| title_short |
The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy |
| title_full |
The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy |
| title_fullStr |
The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy |
| title_full_unstemmed |
The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy |
| title_sort |
ca2+-activated cation channel trpm4 is a positive regulator of pressure overload-induced cardiac hypertrophy |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2021-06-01 |
| description |
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. |
| topic |
mechanosensitive channels left ventricular hypertrophy cardiovascular disease Ca2+/calmodulin-dependent protein kinase II |
| url |
https://elifesciences.org/articles/66582 |
| work_keys_str_mv |
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doaj-e5eac8e184ce43e695d6df669f74745c2021-06-30T13:08:49ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.66582The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophyYang Guo0Ze-Yan Yu1Jianxin Wu2Hutao Gong3Scott Kesteven4Siiri E Iismaa5Andrea Y Chan6Sara Holman7Silvia Pinto8Andy Pironet9Charles D Cox10Robert M Graham11Rudi Vennekens12Michael P Feneley13Boris Martinac14https://orcid.org/0000-0001-8422-7082Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, Australia; Cardiac Physiology and Transplantation Division, Victor Chang Cardiac Research Institute, Sydney, Australia; St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, AustraliaMolecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, Australia; Cardiac Physiology and Transplantation Division, Victor Chang Cardiac Research Institute, Sydney, Australia; St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, AustraliaMolecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, AustraliaCardiac Physiology and Transplantation Division, Victor Chang Cardiac Research Institute, Sydney, AustraliaCardiac Physiology and Transplantation Division, Victor Chang Cardiac Research Institute, Sydney, Australia; St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, AustraliaMolecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, Australia; St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, AustraliaMolecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, AustraliaMolecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, AustraliaLaboratory of Ion Channel Research, Department of Molecular and Cellular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium; TRP Research Platform Leuven (TRPLe), Katholieke Universiteit Leuven, Leuven, BelgiumLaboratory of Ion Channel Research, Department of Molecular and Cellular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium; TRP Research Platform Leuven (TRPLe), Katholieke Universiteit Leuven, Leuven, BelgiumMolecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, Australia; St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, AustraliaMolecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, Australia; St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, AustraliaLaboratory of Ion Channel Research, Department of Molecular and Cellular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium; TRP Research Platform Leuven (TRPLe), Katholieke Universiteit Leuven, Leuven, BelgiumCardiac Physiology and Transplantation Division, Victor Chang Cardiac Research Institute, Sydney, Australia; St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia; Department of Cardiology, St Vincent’s Hospital, Sydney, AustraliaMolecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, Australia; St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, AustraliaPathological 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.https://elifesciences.org/articles/66582mechanosensitive channelsleft ventricular hypertrophycardiovascular diseaseCa2+/calmodulin-dependent protein kinase II |