The Study On The Mechanism Of The Protective Effects Of Polyunsaturated Fatty Acids On Macroangiopathy

Objective To investigate the mechanisms of the protective effect of arachidonic acid on lipotoxicity induced by saturated free fatty acids (SFFAs) in endothelial ECV-304 cells. Methods ECV-304 cells were treated with 200 umol/L of SFFAs including palmitic acid (PA) and stearic acid (SA), 5 umol/L of polyunsaturated free fatty acid, arachidonic acid (AA), and NDGA, the lipoxygenaseinhibitor, indomethacin (Indo), the cyclooxygenase inhibitor, ketoconazole (Ket), the P450 enzyme inhibitor, nifedipine (Nif), the 1,4-dihydropyridine-type Ca2+ channel blocker, and staurosporine (St), a potent inhibitor of calcium-dependent protein kinase, respectively, for 48h, and then the cell viability was assessed using MTT method. Results (1) The cell viability was 55.2+3.4% and 56.1+3.9%, respectively, after exposure to 200 umol/L PA or SA for 48h, which were significantly decreased as compared with the control (P<0.01); (2) AA stimulated the cell proliferation at 5 umol/L to 138%+4.2%, and was significantly increased (P<0.05) compared with the control; (3) NADG, Indo, Ket, Nif and St themselves did not affect the cell viability, while NADG, Nif and St could completely prevent the protective effects of AA on the lipotoxicity induced by PA. Conclusion AA protect ECV-304 cells against lipotoxicity induced by PA through its metabolites of lipoxygenase, and activation of calcium system.