New publication: Role of PKC isoforms in cardiomyocyte hypertrophy

20.1.2021
Our article entitled “Pharmacological protein kinase C modulators reveal a pro-hypertrophic role for novel protein kinase C isoforms in human induced pluripotent stem cell-derived cardiomyocytes” has been published in Frontiers in Pharmacology.

In this study, we show that pharmacological protein kinase C (PKC) activation induces cardiomyocyte hypertrophy via activation of novel PKC isoforms. Both neonatal rat ventricular cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes exhibit similar hypertrophic responses to PKC modulators, but distinct PKC-independent mechanisms of endothelin-1-induced hypertrophy.

Hypertrophy of cardiomyocytes is initially a compensatory mechanism to cardiac overload for example in high blood pressure, but when prolonged, it leads to maladaptive myocardial remodeling, which impairs cardiac function and causes heart failure. Previous studies suggested controversial roles for both classical and novel PKC isoforms in hypertrophy of rodent cardiomyocytes, whereas the role of PKC in hypertrophy of human cardiomyocytes had not been studied before. In this study, we used pharmacological tools to elucidate the role of classical and novel PKC isoforms in cardiomyocyte hypertrophy both in neonatal rat ventricular myocytes and in human induced pluripotent stem cell-derived cardiomyocytes in vitro. As readouts, we measured hypertrophic gene expression and cardiomyocyte morphology.

Because PKC modulators are being developed for the treatment of many diseases, such as cancer and Alzheimer’s disease, it is crucial to characterize their cardiac effects. The pro-hypertrophic effect of PKC activators reported in this study should be considered when developing therapeutic PKC-targeted compounds.

Link to the online version of the article: https://doi.org/10.3389/fphar.2020.553852