Effects of cyclosporine A on angiotensin II-induced cardiomyocyte hypertrophy in neonatal rats

Abstract

The effects of cyclosporine A (CsA) on Angiontensin II (Ang II)-induced protein contents, c-fos protein levels and cytosolic Ca²⁺ level ([Ca²⁺]i) in cultured cardiomyocytes of neonatal rats were observed. Total protein contents were determined by Bradford method. The expression of c-fos protein was detected by Western blot. [Ca²⁺]i labeled with fluorescent probe Fluo-3/AM was measured under a laser scanning confocal microscope. The results revealed that as compared with control, the total protein contents were increased in cardiomyocytes treated with Ang II (10⁻⁷ mol/ L), which could be inhibited by CsA in a dose-dependent manner. It was found that Ang II could increase the c-fos protein expression, which could be inhibited by CsA in a dose-dependent manner. Ang II induced the [Ca²⁺]i elevation in cardiomyocytes. CsA did not influence the resting intracellular Ca²⁺, but inhibited significantly the Ang II-induced [Ca²⁺]i elevation. It was concluded that CsA can suppress the Ang II-induced c-fos protein expression and [Ca²⁺]i elevation in single cardiomyocyte, which might pay a role in the prevention of Ang II-induced cardiomyocyte hypertrophy by CsA.

Keywords

cardiomyocyte hypertrophy / angiotensin II / cyclosporine A / c-fos / Ca²⁺

References

[1] MolkentinJ D, LuJ R, AntosC L, et al. . A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell, 1998, 93: 215-215

[2] BakerK M, CherinM I, WixsonS K, et al. . Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats. Am J Physiol, 1990, 259: H324-H324

[3] BakerK M, AcetoJ F. Angiotension II stimulation of protein synthesis and cell growth in chick heart cell. Am J Physiol, 1990, 259: H610-H610

[4] TaigenT, De WindtL J, LimH W, et al. . Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A, 2000, 97(3): 1196-1196

[5] PianoM R. Cellular and signaling mechanisms of cardiac hypertrophy. J Cardiovasc Nurs, 1994, 8(4): 1-1