Effect of SKF‑96365 on cardiomyocyte hypertrophy induced by angiotensin II

Abstract

Angiotensin II (Ang II) is an important bioactive peptide in the renin-angiotensin system, and it can contribute to cell proliferation and cardiac hypertrophy. Dysfunctions in transient receptor potential canonical (TRPC) channels are involved in many types of cardiovascular diseases. The aim of the present study was to investigate the role of the TRPC channel inhibitor SKF-96365 in cardiomyocyte hypertrophy induced by Ang II and the potential mechanisms of SKF-96365. H9c2 cells were treated with different concentrations of Ang II. The expression levels of cardiomyocyte hypertrophy markers and TRPC channel-related proteins were also determined. The morphology and surface area of the H9c2 cells, the expression of hypertrophic markers and TRPC channel-related proteins and the [3H] leucine incorporation rate were detected in the Ang II-treated H9c2 cells following treatment with the TRPC channel inhibitor SKF-96365. The intracellular Ca2+ concentration was tested by flow cytometry. The present results suggested that the surface area of H9c2 cells treated with Ang II was significantly increased compared with untreated H9c2 cells. The fluorescence intensity of α-actinin, the expression of hypertrophic markers and TRPC-related proteins, the [3H] leucine incorporation rate and the intracellular Ca2+ concentration were all markedly increased in the Ang II-treated H9c2 cells but decreased following SKF-96365 treatment. The present results suggested that Ang II induced cardiomyocyte hypertrophy in H9c2 cells and that the TRPC pathway may be involved in this process. Therefore, SKF-96365 can inhibit cardiomyocyte hypertrophy induced by Ang II by suppressing the TRPC pathway. The present results indicated that TRPC may be a therapeutic target for the development of novel drugs to treat cardiac hypertrophy.