PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia

Abstract Ischaemic heart disease is the world’s leading cause of mortality. Survival rates from acute myocardial infarction (MI) have improved in recent years; however, this has led to an increase in the prevalence of heart failure (HF) due to chronic remodelling of the infarcted myocardium, for whi...

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Autores principales:	Nicholas Stafford, Min Zi, Florence Baudoin, Tamer M. A. Mohamed, Sukhpal Prehar, Daria De Giorgio, Elizabeth J. Cartwright, Roberto Latini, Ludwig Neyses, Delvac Oceandy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4179615b5a6949a8af26a24a91ac9b86
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spelling	oai:doaj.org-article:4179615b5a6949a8af26a24a91ac9b862021-12-02T14:01:38ZPMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia10.1038/s41598-021-81170-22045-2322https://doaj.org/article/4179615b5a6949a8af26a24a91ac9b862021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81170-2https://doaj.org/toc/2045-2322Abstract Ischaemic heart disease is the world’s leading cause of mortality. Survival rates from acute myocardial infarction (MI) have improved in recent years; however, this has led to an increase in the prevalence of heart failure (HF) due to chronic remodelling of the infarcted myocardium, for which treatment options remain poor. We have previously shown that inhibition of isoform 4 of the plasma membrane calcium ATPase (PMCA4) prevents chronic remodelling and HF development during pressure overload, through fibroblast mediated Wnt signalling modulation. Given that Wnt signalling also plays a prominent role during remodelling of the infarcted heart, this study investigated the effect of genetic and functional loss of PMCA4 on cardiac outcomes following MI. Neither genetic deletion nor pharmacological inhibition of PMCA4 affected chronic remodelling of the post-MI myocardium. This was the case when PMCA4 was deleted globally, or specifically from cardiomyocytes or fibroblasts. PMCA4-ablated hearts were however less prone to acute arrhythmic events, which may offer a slight survival benefit. Overall, this study demonstrates that PMCA4 inhibition does not affect chronic outcomes following MI.Nicholas StaffordMin ZiFlorence BaudoinTamer M. A. MohamedSukhpal PreharDaria De GiorgioElizabeth J. CartwrightRoberto LatiniLudwig NeysesDelvac OceandyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicholas Stafford Min Zi Florence Baudoin Tamer M. A. Mohamed Sukhpal Prehar Daria De Giorgio Elizabeth J. Cartwright Roberto Latini Ludwig Neyses Delvac Oceandy PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia
description	Abstract Ischaemic heart disease is the world’s leading cause of mortality. Survival rates from acute myocardial infarction (MI) have improved in recent years; however, this has led to an increase in the prevalence of heart failure (HF) due to chronic remodelling of the infarcted myocardium, for which treatment options remain poor. We have previously shown that inhibition of isoform 4 of the plasma membrane calcium ATPase (PMCA4) prevents chronic remodelling and HF development during pressure overload, through fibroblast mediated Wnt signalling modulation. Given that Wnt signalling also plays a prominent role during remodelling of the infarcted heart, this study investigated the effect of genetic and functional loss of PMCA4 on cardiac outcomes following MI. Neither genetic deletion nor pharmacological inhibition of PMCA4 affected chronic remodelling of the post-MI myocardium. This was the case when PMCA4 was deleted globally, or specifically from cardiomyocytes or fibroblasts. PMCA4-ablated hearts were however less prone to acute arrhythmic events, which may offer a slight survival benefit. Overall, this study demonstrates that PMCA4 inhibition does not affect chronic outcomes following MI.
format	article
author	Nicholas Stafford Min Zi Florence Baudoin Tamer M. A. Mohamed Sukhpal Prehar Daria De Giorgio Elizabeth J. Cartwright Roberto Latini Ludwig Neyses Delvac Oceandy
author_facet	Nicholas Stafford Min Zi Florence Baudoin Tamer M. A. Mohamed Sukhpal Prehar Daria De Giorgio Elizabeth J. Cartwright Roberto Latini Ludwig Neyses Delvac Oceandy
author_sort	Nicholas Stafford
title	PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia
title_short	PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia
title_full	PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia
title_fullStr	PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia
title_full_unstemmed	PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia
title_sort	pmca4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4179615b5a6949a8af26a24a91ac9b86
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PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia

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