Oncotarget

Research Papers:

Acute atorvastatin treatment restores the cardioprotective effects of ischemic postconditioning in hyperlipidemic rats

Tao Sun, Hong-Ju Zhang, Chayakrit Krittanawong, Su Wang, Ying Tao, Zhao Li, Qiancheng Yin, Donghua Zhang, Qian Wang, Ji Huang, Jingmei Zhang, Zhizhong Li and Yutong Cheng _

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Oncotarget. 2017; 8:55187-55193. https://doi.org/10.18632/oncotarget.19232

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Abstract

Tao Sun1, Hong-Ju Zhang2, Chayakrit Krittanawong3, Su Wang1, Ying Tao1, Zhao Li1, Qiancheng Yin1, Donghua Zhang1, Qian Wang1, Ji Huang1, Jingmei Zhang1, Zhizhong Li1 and Yutong Cheng1

1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

2Division of Ultrasound, Fu Wai Hospital, National Center for Cardiovascular Diseases, Beijing, China

3Department of Internal Medicine, Icahn School of Medicine at Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA

Correspondence to:

Yutong Cheng, email: [email protected]

Keywords: ischemic postconditioning, statin, atorvastatin, hyperlipidemia, infarct size-limiting effect

Received: November 24, 2016     Accepted: June 16, 2017     Published: July 14, 2017

ABSTRACT

Background: Ischemic Postconditioning (IPC) reduces ischemia/reperfusion (I/R) injury under normal conditions. HMG-CoA reductase inhibitors (statins), which inhibit the synthesis of mevalonate, can interfere with the cardioprotective effect of IPC. However, the beneficial role of IPC in hyperlipidemic patients, post-acute administration of statins remains unknown. This study was to determine if acute administration of atorvastatin affect the infarct size-limiting effect of IPC in hyperlipidemic rats.

Results: Compared to control group, infarct size decreased more significantly in atorvastatin+IPC and atorvastatin+IPC+wortmannin groups than IPC or atorvastatin+IPC+PD98059 groups. Phosphorylation of PI3K/Akt was attenuated in atorvastatin + IPC+ wortmannin group, phosphorylation of P42 MAPK/ERK was increased in atorvastatin+IPC and atorvastatin+IPC+wortmannin groups.

Materials and Methods: Ninety four-weeks old male SD rats fed with cholesterol enriched diet for six weeks were randomized into nine groups (n = 10/group) - sham group, control group, IPC group, atorvastatin group, wortmannin group, PD98059 group, atorvastatin+IPC group, atorvastatin+IPC+wortmannin group and atorvastatin+IPC+PD98059 group. Atorvastatin was administered orally 12 hours before myocardial reperfusion.

Conclusions: Post-translational activation of P42 MAPK/ERK, rather than PI3K/Akt, participates in the net protective effect of IPC and atorvastatin in hyperlipidemia.


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