Key result
Aspirin suppressed atherosclerosis progression and increased plaque stability in vivo by activating AP-2α to upregulate IkBα gene expression.
Why the study?
Does aspirin reduce atherosclerotic plaque growth and instability via AP-2α activation in Apoe-/- mice and human subjects?
Does aspirin reduce atherosclerotic plaque growth and instability via AP-2α activation in Apoe-/- mice and human subjects?
Aspirin attenuates atherosclerotic plaque development and instability by activating AP-2α to upregulate IkBα gene expression.
Does not support altering clinical aspirin use; leaves open translation of AP-2α mechanism from mice to humans.
// Jing-Jing Yang 1 , Peng Li 2 , Fu Wang 1 , Wen-Jing Liang 1 , Hui Ma 1 , Yuan Chen 1 , Zhi-Min Ma 3 , Quan-Zhong Li 4 , Qi-Sheng Peng 5 , Yun Zhang 1 and Shuang-Xi Wang 1,2 1 Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, China 2 Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, China 3 Division of Endocrinology, The Second Affiliated Hospital, Soochow University, Suzhou, China 4 Division of Cardiology, The Affiliated Hospital, Guilin Medical University, Guilin, China 5 Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China Correspondence to: Shuang-Xi Wang, email: // Yun Zhang, email: // Keywords : activator protein 2α, aspirin, IkBα, atherosclerosis, Pathology Section Received : March 24, 2016 Accepted : June 17, 2016 Published : July 04, 2016 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.
No takes yet. Share an insight, caveat, or question.
Yang et al. (2016) studied Atherosclerosis. Aspirin was evaluated on Atherosclerotic plaque growth and instability. Aspirin suppressed atherosclerosis progression and increased plaque stability in vivo by activating AP-2α to upregulate IkBα gene expression.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: