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

作者：Yang, Jing-Jing; Li, Peng; Wang, Fu; Liang, Wen-Jing; Ma, Hui; Chen, Yuan; Ma, Zhi-Min; Li, Quan-Zhong; Peng, Qi-Sheng; Zhang, Yun^*; Wang, Shuang-Xi^*

来源：Oncotarget, 2016, 7(33): 52729-52739.

DOI：10.18632/oncotarget.10400

• activator protein 2 alpha
• aspirin
• IkB alpha
• atherosclerosis
• Pathology Section

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 2 alpha (AP-2 alpha) 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-2 alpha reversed the inhibitory effects of aspirin on atherosclerosis in Apoe(-/-) mice. Mechanically, aspirin increased AP-2 alpha phosphorylation and its activity, upregulated IkB alpha mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2 alpha completely abolished aspirin-induced upregulation of IkB alpha levels and inhibition of oxidative stress in Apoe(-/-) mice. Clinically, conventional doses of aspirin increased AP-2 alpha phosphorylation and IkB alpha protein expression in humans subjects. Conclusion: Aspirin activates AP-2 alpha to upregulate IkB alpha gene expression, resulting in attenuations of plaque development and instability in atherosclerosis.

• 出版日期2016-8-16
• 单位桂林医学院; 吉林大学; 山东大学; 苏州大学; 新乡医学院