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