S-EPMC5288144 - Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo. - OmicsDI

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

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 2? (AP-2?) 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? reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. Mechanically, aspirin increased AP-2? phosphorylation and its activity, upregulated IkB? mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2? completely abolished aspirin-induced upregulation of IkB? levels and inhibition of oxidative stress in Apoe-/- mice. Clinically, conventional doses of aspirin increased AP-2? phosphorylation and IkB? protein expression in humans subjects.

Conclusion

Aspirin activates AP-2? to upregulate IkB? gene expression, resulting in attenuations of plaque development and instability in atherosclerosis.

SUBMITTER: Yang JJ

PROVIDER: S-EPMC5288144 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Yang Jing-Jing JJ Li Peng P Wang Fu F Liang Wen-Jing WJ Ma Hui H Chen Yuan Y Ma Zhi-Min ZM Li Quan-Zhong QZ Peng Qi-Sheng QS Zhang Yun Y Wang Shuang-Xi SX

Oncotarget 20160801 33

<h4>Aims</h4>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.<h4>Methods and results</h4>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 stabilit ...[more]

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