Submitted on February 13, 2008
Revised on May 22, 2008
Accepted on June 2, 2008
Induction of paraoxonase 1 and apolipoprotein A1 gene expression by aspirin
Priscilla Jaichander, Krithika Selvarajan, Mahdi Garelnabi, and Sampath Parthasarathy
Surgery, Ohio State University, Columbus, OH 43210
Corresponding Author: spartha{at}osumc.edu
Low dose aspirin therapy has become a standard in the treatment of cardiovascular diseases. Aspirin has been shown to inhibit atherosclerosis in mouse models. In order to determine the mechanisms by which aspirin might inhibit atherosclerosis, we incubated HEPG2 cells and rat primary hepatocytes with aspirin or salicylic acid and noted an increase in paraoxonase 1(PON1) activity in the medium, together with an induction of PON 1 and apolipoprotein A1 (APO A1) gene expression. Mice treated with aspirin also showed a two fold increase in plasma PON 1 activity and a significant induction of both PON1 and APO A1 gene expression in the liver. The induction of PON 1 gene in cell culture was accompanied by an increase in arylhydrocarbon receptor (AhR) gene expression. Accordingly, aspirin treatment of AhR-/- animals failed to induce PON 1 gene expression. We previously suggested that aspirin might be hydrolyzed by serum PON 1 and could account for its short plasma half-life of 10 minutes. Taken together with the current studies, we suggest the anti-atherosclerotic effects of aspirin might be mediated by its hydrolytic product salicylate and the induction of PON 1 and APO A1 might be important in the cardio-protective effects of aspirin.
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