Regulations of the key mediators in inflammation and atherosclerosis by aspirin in human macrophages.
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-kappaB 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-kappaB 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-kappaB, and increasing the cholesterol efflux through inducing expressions of ABCA1 and SR-BI.
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
Li
L
Lu
Hong
H
Liu
Jiahe
J
Peng
Lin
L
Gan
Lili
L
Shen
Qian
Q
Zhang
Liangpeng
L
Li
Li
L
Zhang
Chang
C
Su
Yu
Y
Jiang
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000378:metabolism / Q000494:pharmacology*; D050197:Atherosclerosis; D018955:CD36 Antigens / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018955:CD36 Antigens; D016328:NF-kappa B; D002784:Cholesterol; D020780:Matrix Metalloproteinase 9; D001241:Aspirin