30 November 2023
New potential therapy for cardiac hypertrophy
Published online 6 April 2016
Scientists find a way to inhibit a membrane protein that triggers a heart disease.
Inhibiting the activity of a specific calcium-regulating membrane protein may prevent the thickening of heart muscle tissues, a disorder known as cardiac hypertrophy, a new study finds1.
This insight could potentially be useful for developing therapies for the disorder.
The role of calcium in the regulation of specific heart cells, such as cardiac fibroblasts, is related to cardiac hypertrophy, but its mechanism is still unknown.
Now scientists from the University of Manchester, UK, J. David Gladstone Research Institutes, USA, and Zagazig University, Egypt, confirm that the plasma membrane calcium ATPase isoform 4 (PMCA4) regulates calcium signal in adult mouse cardiac fibroblasts.
To investigate further, the scientists deleted Pmca4, the gene that encodes PMCA4 in mice. The mice lacking PMCA4 produced secreted frizzled related protein 2 (sFRP2) in cardiac fibroblasts. The mice treated with anti-sFRP2 antibody lost their ability to combat cardiac hypertrophy, suggesting an anti-hypertrophic role for sFRP2.
The mice with the deleted gene were found to be protected against any heart dysfunction induced by cardiac pressure overload. In addition, inhibiting PMCA4 with aurintricarboxylic acid, a drug-like molecule, increased the levels of sFRP2 and suppressed cardiac hypertrophy in mice, according to the researchers.
“This research reveals a new insight into the therapeutic approach for heart disease, by targeting cardiac fibroblasts”, says principal investigator Delvac Oceandy.
- Mohamed, T. M. A. et al. The plasma membrane calcium ATPase 4 signalling in cardiac fibroblasts mediates cardiomyocyte hypertrophy. Nat. Commun. 7, 11074 (2016).