Regulations of the key mediators in inflammation and atherosclerosis by Aspirin in human macrophages

Lipids in Health and Disease

Research

Li Lu¹  Lili Shen¹  Liangpeng Li¹  Yu Jiang¹  Lin Gan¹  Qian Zhang¹  Jiahe Peng¹  Li Zhang¹  Chang Su¹  Hong Liu² 

[1] Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, 400038, Chongqing, China;Department of Hematology, Xin-Qiao Hospital, Third Military Medical University, 400037, Chongqing, China;

关键词: Acetyl Salicylic Acid;    Foam Cell;    Cholesterol Efflux;    Reverse Cholesterol Transport;    Acetyl Salicylic Acid;   

DOI  :  10.1186/1476-511X-9-16

 received in 2009-12-21, accepted in 2010-02-06,  发布年份 2010

来源: Springer

【 摘 要 】

Although its role to prevent secondary cardiovascular complications has been well established, how acetyl salicylic acid (ASA, aspirin) regulates certain key molecules in the atherogenesis is still not known. Considering the role of matrix metalloproteinase-9 (MMP-9) to destabilize the atherosclerotic plaques, the roles of the scavenger receptor class BI (SR-BI) and ATP-binding cassette transporter A1 (ABCA1) to promote cholesterol efflux in the foam cells at the plaques, and the role of NF-κB in the overall inflammation related to the atherosclerosis, we addressed whether these molecules are all related to a common mechanism that may be regulated by acetyl salicylic acid. We investigated the effect of ASA to regulate the expressions and activities of these molecules in THP-1 macrophages. Our results showed that ASA inhibited MMP-9 mRNA expression, and caused the decrease in the MMP-9 activities from the cell culture supernatants. In addition, it inhibited the nuclear translocation of NF-κB p65 subunit, thus the activity of this inflammatory molecule. On the contrary, acetyl salicylic acid induced the expressions of ABCA1 and SR-BI, two molecules known to reduce the progression of atherosclerosis, at both mRNA and protein levels. It also stimulated the cholesterol efflux out of macrophages. These data suggest that acetyl salicylic acid may alleviate symptoms of atherosclerosis by two potential mechanisms: maintaining the plaque stability via inhibiting activities of inflammatory molecules MMP-9 and NF-κB, and increasing the cholesterol efflux through inducing expressions of ABCA1 and SR-BI.

【 授权许可】

Unknown   
© Lu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.