Role Ecosapantaenoic Acid(EPA) on the gene expression of Peroxisome Proliferators Activated Receptors

Introduction: Defect in the cholesterol homeostasis in macrophage as well as converting them to foam cells is one of the most important factors in the initiation and progression of atherosclerosis. Many genes and transcription factors like Peroxisome Proliferators Activated Receptors are involved in cholesterol homeostasis in these cells. N-3 fatty acids are one of the most important factors regulating the expression of these genes and thus can affect intracellular metabolism of cholesterol, initiation, and progression of atherosclerosis. Ecosapantalenic acid (EPA) among N-3 fatty acids in the diet is the most frequent .Therefore studies investigating its effect on the gene expression have great significance. Methods: In this study, LDL was isolated by density gradient ultra centrifugation method and then was acetylated with sodium acetate. To convert macrophages into foam cells, macrophages were incubated with Acetylated LDL in a concentration of 50g / mL. The effects of EPA and the synthetic ligand (Wy14643) on the gene expression of PPAR gene in foam cells derived from THP-1 cells were investigated by Real time PCR technique. Results: treatment of cells with EPA caused a decrease in cellular cholesterol, free cholesterol and cholesterol ester (P≤0.05). EPA and wy14643 significantly increased gene expression of PPAR in these cells. Conclusion: It seems that this fatty acid had unique and special effect on the gene expression and lipid metabolism in foam cells. Also, mechanisms other than PPAR such as LXR can also be effective on intracellular cholesterol homeostasis in foam cells. In order to gain more information regarding effects of this fatty acids, simultaneous study of genes involved in lipid metabolism within the foam cell will be needed.