1. Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo.
- Author
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Yang JJ, Li P, Wang F, Liang WJ, Ma H, Chen Y, Ma ZM, Li QZ, Peng QS, Zhang Y, and Wang SX
- Subjects
- Animals, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Apolipoproteins E genetics, Apolipoproteins E metabolism, Atherosclerosis genetics, Atherosclerosis metabolism, Cells, Cultured, Gene Expression drug effects, Humans, Male, Mice, Knockout, Muscle, Smooth, Vascular cytology, Myocytes, Smooth Muscle drug effects, Myocytes, Smooth Muscle metabolism, NF-KappaB Inhibitor alpha genetics, NF-KappaB Inhibitor alpha metabolism, Phosphorylation drug effects, Plaque, Atherosclerotic genetics, Plaque, Atherosclerotic metabolism, RNA Interference, Transcription Factor AP-2 genetics, Aspirin pharmacology, Atherosclerosis prevention & control, Plaque, Atherosclerotic prevention & control, Transcription Factor AP-2 metabolism
- 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., Competing Interests: There is no conflict of interest.
- Published
- 2016
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