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AMPK-mediated Cardioprotection of Atorvastatin Relates to the Reduction of Apoptosis and Activation of Autophagy in Infarcted Rat Hearts

AMPK-mediated Cardioprotection of Atorvastatin Relates to the Reduction of Apoptosis and Activation of Autophagy in Infarcted Rat Hearts

Qing Li, Qiu-Ting Dong, Yue-Jin Yang, Xia-Qiu Tian, Chen Jin, Pei-Sen Huang, Lei-Pei Jiang, Gui-Hao Chen

Am J Transl Res. 2016 Oct 15;8(10):4160-4171.

PMID: 27830000

Abstract:

Atorvastatin (ATV) has an important pro-survival role in cardiomyocytes after acute myocardial infarction (AMI). The objectives of this study were to: 1) determine whether ATV could affect autophagy of cardiomyocytes via the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, and 2) investigate the balance between autophagy and apoptosis pathways. Male Wistar rats (n = 100) were randomly divided into sham, control, ATV, Compound C, and ATV+ Compound C groups. In this AMI model, drug treatments were administered for 1 week before induction of MI by surgical ligation, and measurements were taken 1 and 4 weeks after AMI induction. Transthoracic echocardiography showed that the ejection fraction in the ATV group increased by 11.7% ± 6.83% over the control group 4 weeks after AMI. The fibrosis, infarcted area, and inflammatory level were determined by pathological and histological studies; these were found to be decreased substantially with ATV treatment (P<0.05). The expression of apoptotic, autophagic, and AMPK pathway proteins was detected by immunohistochemical staining and western blotting, while expression of their corresponding genes was measured with real-time polymerase chain reaction (PCR). ATV treatment increased AMPK/mTOR activity and the expression of autophagic protein LC3 in infarcted myocardium (P<0.05). The treatment also inhibited induction of pro-apoptotic protein Bax. AMPK inhibitor Compound C reversed these beneficial effects. In conclusion, ATV improves survival of cardiomyocytes and decreases alterations in morphology and function of infarcted hearts by inducing autophagy and inhibiting apoptosis through the activation of AMPK/mTOR pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP693793532	Atorvastatin Related Compound C		693793-53-2	Price

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