The Effect of Selective Cyclooxygenase-2 Inhibition DFU in Atherogenesis

Objective To investigate COX-2,the status of internal elastic lamina,as well as collagen content in atherogenesis in a cholesterol-fed rabbit model,and whether inhibition of COX-2,by selective inhibitor,DFU [5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)-phenyl-2-(5H)-furanone],could block the progression of atherosclerosis.Methods 42 NZW(six weeks old) were fed with the high lipid diet for 1 week.The effect of DFU,a selective COX-2 inhibitor,on the progression of atherosclerosis and randomLy separated into 4 groups according to the elevation of plasma cholesterol to avoid grouping bias.All rabbits were gavaged with either vehicle or DFU for different dosis four weeks as the high lipid diet continued.Three random selected aortic arteries(from the root of aortic arch to the illiac bifurcation) from each group were excised and snap-frozen in liquid nitrogen.The fomer 1/3 of the aortic arch was for HE staining and the latter 2/3 was homogenized for gelatinase zymography and western blotting analysis of MMP-2.The rest aortic arteries of each group were sectioned logitudinally and fixed in 4% paraformaldehyde for Sudan staining.Aortic intima was photographed and the ratio of atherosclerotic area to the whole intima area was analysized using Matlab software.Results The expression of COX-2 was increased in the proliferated intima during atherogenesis.DFU had no effect on body weight,plasma lipid parameters,and the expression or activity of MMP-2 of the aortic arch homogenate in the 4 groups.No significant difference on the ratio of atherosclerotic area between group 0 and the 3 DFU-administration groups was detected(P 0.50).The ratios(mean±SE) was 0.330±0.052(n=7) for group 0,0.273 ± 0.042(n=6) for group 1,0.314 ± 0.089(n=8) for group 2,0.288 ± 0.036(n=9) for group 3.Conclusion Despite that COX-2 was associated with the early progression of atherosclerosis,selective inhibition of COX-2 by DFU did not block the progression of atherosclerosis.