title: Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Aspirin activates AP-2α to upregulate IkBα gene expression, resulting in attenuations of plaque development and instability in atherosclerosis.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Liang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ma
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Endocrinology, The Second Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Ma
authors.affiliation: Division of Cardiology, The Affiliated Hospital, Guilin Medical University, Guilin, China.
authors.forename: Quan-Zhong
authors.initials: QZ
authors.lastname: Li
authors.affiliation: Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China.
authors.forename: Qi-Sheng
authors.initials: QS
authors.lastname: Peng
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.|Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, China.
authors.forename: Shuang-Xi
authors.initials: SX
authors.lastname: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D034622:RNA Interference; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001057:Apolipoproteins E; D050656:Transcription Factor AP-2; D000072000:NF-KappaB Inhibitor alpha; D001241:Aspirin
keywords: IkBα; Pathology Section; activator protein 2α; aspirin; atherosclerosis