Abstract
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.
Highlights
The effects of acetyl salicylic acid (Aspirin, ASA) and other drugs in the prevention of the secondary cardiovascular complications are well known
Considering the potential connections among matrix metalloproteinase-9 (MMP-9), scavenger receptor class BI (SR-BI), ATP-binding cassette transporter A1 (ABCA1) and NF-B in related to inflammation and atherosclerosis, and the regulatory roles played by ASA in these mechanisms, we investigated the effects of ASA on the expressions of these molecules using highly relevant human macrophages
When the control or drug-treated cells were harvested and their mRNA levels for MMP-9 were analyzed by reverse transcriptionpolymerase chain reaction (RT-PCR), we observed that acetyl salicylic acid inhibited MMP-9 mRNA expression in a dose-dependent manner (Figure 2)
Summary
The effects of acetyl salicylic acid (Aspirin, ASA) and other drugs in the prevention of the secondary cardiovascular complications are well known. Atherosclerosis is an inflammatory disease [4] and the atherosclerotic plaques are formed by the accumulation. It will be interesting to know whether other inflammatory mediators such as NF-B play any roles in the mechanisms of atherosclerosis. In this regard, aspirin exert its function mainly by suppressing the vascular inflammation and stabilizing early atherosclerotic plaques [9], as showed earlier from the study by Cyrus’s group. Further studies from the same group showed that ASA reduced the progression of atherosclerosis, and decreased the contents of cholesterols foam cells [10]. Since SR-BI and ABCA1 are the most important protein members determining the contents of foam cells, they may be the targets of ASA
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