Projects per year
Abstract
The heart responds to pathological overload through myocyte hypertrophy. Here we show that this response is regulated by cardiac fibroblasts via a paracrine mechanism involving plasma membrane calcium ATPase 4 (PMCA4). Pmca4 deletion in mice, both systemically and specifically in fibroblasts, reduces the hypertrophic response to pressure overload; however, knocking out Pmca4 specifically in cardiomyocytes does not produce this effect. Mechanistically, cardiac fibroblasts lacking PMCA4 produce higher levels of secreted frizzled related protein 2 (sFRP2), which inhibits the hypertrophic response in neighbouring cardiomyocytes. Furthermore, we show that treatment with the PMCA4 inhibitor aurintricarboxylic acid (ATA) inhibits and reverses cardiac hypertrophy induced by pressure overload in mice. Our results reveal that PMCA4 regulates the development of cardiac hypertrophy and provide proof of principle for a therapeutic approach to treat this condition.
Original language | English |
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Article number | 11074 |
Journal | Nature Communications |
Volume | 7:1107 |
DOIs | |
Publication status | Published - 29 Mar 2016 |
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Dive into the research topics of 'The Plasma Membrane Calcium ATPase 4 Signalling in Cardiac Fibroblasts Mediates Cardiomyocyte Hypertrophy'. Together they form a unique fingerprint.Projects
- 3 Finished
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Signal Modulation in Cardiac Fibroblasts by the Plasma Membrane Calcium ATPase4 (PMCA4) as a Novel Approach to Control Myocardial Hypertrophy.
Oceandy, D. (PI), Cartwright, E. (CoI), Mohamed, T. (CoI) & Neyses, L. (CoI)
1/05/13 → 31/10/16
Project: Research
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The Protective Role of Interleukin-10 Receptor Signalling in the Heart.
Oceandy, D. (PI), Muller, W. (CoI) & Neyses, L. (CoI)
1/09/11 → 28/02/14
Project: Research
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The Role of RASSF1A (Ras Association Domain Family Protein 1A) and Mst2 (Mammalian Sterile 20-Like 2) Signalling Network in Myocardial Hypertrophy.
Oceandy, D. (PI) & Neyses, L. (CoI)
1/04/10 → 31/03/15
Project: Research