PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia
Open Access
- 15 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 11 (1), 1-17
- https://doi.org/10.1038/s41598-021-81170-2
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.Funding Information
- British Heart Foundation (PG/16/77/32400)
- Medical Research Council (MR/P015816/1)
This publication has 58 references indexed in Scilit:
- STIM1 is required for attenuation of PMCA-mediated Ca2+clearance during T-cell activationThe EMBO Journal, 2012
- Transforming growth factor (TGF)-β signaling in cardiac remodelingJournal of Molecular and Cellular Cardiology, 2011
- Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activationThe EMBO Journal, 2011
- New insights into the molecular phenotype of eccentric hypertrophyJournal of Molecular and Cellular Cardiology, 2010
- Active Wnt signaling in response to cardiac injuryBasic Research in Cardiology, 2010
- Secreted Frizzled-related protein 2 is a procollagen C proteinase enhancer with a role in fibrosis associated with myocardial infarctionNature, 2008
- Characterization of the inflammatory and fibrotic response in a mouse model of cardiac pressure overloadHistochemistry and Cell Biology, 2008
- Identification and characterization of a novel Schwann and outflow tract endocardial cushion lineage-restricted periostin enhancerDevelopmental Biology, 2007
- Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repairProceedings of the National Academy of Sciences of the United States of America, 2007
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001