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Int J Med Sci. 2018 Oct 20;15(13):1508-1516. doi: 10.7150/ijms.28106. eCollection 2018.

Simvastatin Protects Heart from Pressure Overload Injury by Inhibiting Excessive Autophagy.

Author information

1
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
2
Department of Cardiology, PLA Army General Hospital, No.5 Nanmen Cang, Dongcheng District, Beijing, 100700, China.
3
Department of Cardiology, Beijing Chest Hospital Heart Center, Capital Medical University, No.9. Beiguan Grand Street, Tongzhou District, Beijing, 101149, China.
4
Division of Cardiology, Second Affiliated Hospital of JiaoTong University, Xi'an, 710004, China.

Abstract

Cardiac hypertrophy is an independent predictor of cardiovascular morbidity and mortality. To identify the mechanisms by which simvastatin inhibits cardiac hypertrophy induced by pressure overload, we determined effects of simvastatin on 14-3-3 protein expression and autophagic activity. Simvastatin was administered intragastrically to Sprague-Dawley (SD) rats before abdominal aortic banding (AAB). Neonatal rat cardiomyocytes (NRCs) were treated with simvastatin before angiotensin II (AngII) stimulation. 14-3-3, LC3, and p62 protein levels were determined by western blot. Autophagy was also measured by the double-labeled red fluorescent protein-green fluorescent protein autophagy reporter system. Simvastatin alleviated excessive autophagy, characterized by a high LC3II/LC3I ratio and low level of p62, and blunted cardiac hypertrophy while increasing 14-3-3 protein expression in rats that had undergone AAB. In addition, it increased 14-3-3 expression and inhibited excessive autophagy in NRCs exposed to AngII. Our study demonstrated that simvastatin may inhibit excessive autophagy, increase 14-3-3 expression, and finally exert beneficial effects on cardioprotection against pressure overload.

KEYWORDS:

14-3-3; autophagy; hydroxymethylglutaryl-CoA reductase inhibitors; hypertrophy; simvastatin

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

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