| First Author | Rosenblat M | Year | 2010 |
| Journal | Atherosclerosis | Volume | 210 |
| Issue | 2 | Pages | 414-21 |
| PubMed ID | 20042190 | Mgi Jnum | J:329225 |
| Mgi Id | MGI:7341748 | Doi | 10.1016/j.atherosclerosis.2009.11.044 |
| Citation | Rosenblat M, et al. (2010) Increased macrophage cholesterol biosynthesis and decreased cellular paraoxonase 2 (PON2) expression in Delta6-desaturase knockout (6-DS KO) mice: beneficial effects of arachidonic acid. Atherosclerosis 210(2):414-21 |
| abstractText | OBJECTIVE: To analyze the possible role of arachidonic acid (AA) in macrophage cholesterol biosynthesis and in PON2 expression. METHODS AND RESULTS: We used peritoneal macrophages (MPM) from the 6-DS KO mice that were fed a diet without or with AA. Macrophage cholesterol biosynthesis rate and HMGCoA-reductase mRNA levels were substantially increased, by 98% and 67%, respectively, in MPM from 6-DS KO vs. control (C57BL/6) mice. Furthermore, in the 6-DS KO vs. control mice MPM PON2 expression (mRNA and lactonase activity) was substantially decreased. In line with the above results, AA supplementation to 6-DS KO mice significantly decreased MPM cholesterol biosynthesis rate and HMGCoA-reductase mRNA levels, by 45% and by 4-fold respectively, and increased MPM PON2 lactonase activity and PON2 mRNA, by 119% and 2.3-fold, respectively. Similarly, incubation of control mice MPM or J774A.1 with AA, significantly and dose-dependently decreased cellular cholesterol biosynthesis rate, and increased PON2 expression. These effects were specific for AA since incubation of the cells with docosahexaenoic acid (DHA, another product of 6-DS) had no significant effects on cholesterol biosynthesis rate, and on PON2 activity. CONCLUSIONS: AA decreased macrophage cholesterol biosynthesis rate, and increased PON2 expression. These effects could protect the cells from cholesterol accumulation and oxidation, and from foam cell formation, the hallmark of early atherogenesis. |
