Oncotarget

Research Papers: Pathology:

Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo

Jing-Jing Yang, Peng Li, Fu Wang, Wen-Jing Liang, Hui Ma, Yuan Chen, Zhi-Min Ma, Quan-Zhong Li, Qi-Sheng Peng, Yun Zhang and Shuang-Xi Wang _

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Oncotarget. 2016; 7:52729-52739. https://doi.org/10.18632/oncotarget.10400

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Abstract

Jing-Jing Yang1, Peng Li2, Fu Wang1, Wen-Jing Liang1, Hui Ma1, Yuan Chen1, Zhi-Min Ma3, Quan-Zhong Li4, Qi-Sheng Peng5, Yun Zhang1 and Shuang-Xi Wang1,2

1 Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, China

2 Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, China

3 Division of Endocrinology, The Second Affiliated Hospital, Soochow University, Suzhou, China

4 Division of Cardiology, The Affiliated Hospital, Guilin Medical University, Guilin, China

5 Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China

Correspondence to:

Shuang-Xi Wang, email:

Yun Zhang, email:

Keywords: activator protein 2α, aspirin, IkBα, atherosclerosis, Pathology Section

Received: March 24, 2016 Accepted: June 17, 2016 Published: July 04, 2016

Abstract

Aims: Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. We investigated the roles of transcriptional factor activator protein 2α (AP-2α) in the beneficial effects of aspirin in the growth and vulnerability of atherosclerotic plaque. Methods and Results: In mice deficient of apolipoprotein E (Apoe-/-), aspirin (20, 50 mg/kg/day) suppressed the progression of atherosclerosis in aortic roots and increased the plaque stability in carotid atherosclerotic plaques induced by collar-placement. In vivo lentivirus-mediated RNA interference of AP-2α reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. Mechanically, aspirin increased AP-2α phosphorylation and its activity, upregulated IkBα mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2α completely abolished aspirin-induced upregulation of IkBα levels and inhibition of oxidative stress in Apoe-/- mice. Clinically, conventional doses of aspirin increased AP-2α phosphorylation and IkBα protein expression in humans subjects. Conclusion: Aspirin activates AP-2α to upregulate IkBα gene expression, resulting in attenuations of plaque development and instability in atherosclerosis.


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