Conclusion: Aspirin activates AP-2α to upregulate IkBα gene expression, resulting in attenuations of plaque development and instability in atherosclerosis. Clinically, conventional doses of aspirin increased AP-2α phosphorylation and IkBα protein expression in humans subjects. Furthermore, deficiency of AP-2α completely abolished aspirin-induced upregulation of IkBα levels and inhibition of oxidative stress 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. In vivo lentivirus-mediated RNA interference of AP-2α reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. 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.
#Activator protein Activator
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. Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, ChinaĬorrespondence to: Shuang-Xi Wang, email: Correspondence to: Yun Zhang, email: Keywords: activator protein 2α, aspirin, IkBα, atherosclerosis, Pathology Section Received: March 24, 2016Ībstract Aims: Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, Chinaĭepartment of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, Chinaĭivision of Endocrinology, The Second Affiliated Hospital, Soochow University, Suzhou, Chinaĭivision of Cardiology, The Affiliated Hospital, Guilin Medical University, Guilin, China Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo Jing-Jing Yang1, Peng Li2, Fu Wang1, Wen-Jing Liang1, Hui Ma1, Yuan Chen1, ZhiMin Ma3, Quan-Zhong Li4, Qi-Sheng Peng5, Yun Zhang1 and Shuang-Xi Wang1,2 1