Simvastatin Protects Heart from Pressure Overload Injury by Inhibiting Excessive Autophagy
| Autor: | Jian Zhang, Dongwei Zhang, Zheng Qiangsun, Fei-Fei Su, Wei Zhang, Xue Li, Haichang Wang, Miaoqian Shi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine autophagy Simvastatin Blotting Western Stimulation Pharmacology Muscle hypertrophy Rats Sprague-Dawley 03 medical and health sciences Western blot Animals Medicine Myocytes Cardiac 14-3-3 Cells Cultured Cardioprotection Pressure overload Microscopy Confocal medicine.diagnostic_test business.industry Autophagy Hypertrophy General Medicine Angiotensin II Rats 030104 developmental biology 14-3-3 Proteins business hydroxymethylglutaryl-CoA reductase inhibitors Research Paper medicine.drug |
| Zdroj: | International Journal of Medical Sciences |
| ISSN: | 1449-1907 |
| DOI: | 10.7150/ijms.28106 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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