Relationship Between Heme Oxygenase/Carbon Monoxide And Nitricoxide Synthase/Nitrogen Monoxide System Of Diet-Induced Atherosclerosis In Rabbit

Atherosclerosis is a major contributor to cardiovascular disease, Some hypotheses had been proposed concering the pathogenesis of atherosclerosis , but the real pathogenesis is still unclear so far. The gaseous monoxides nitric oxide and carbon monoxide , generated within the blood vessel wall, have been identified as important cellular messengers involved in the regulation of intracellular cGMP levels, platelet aggregation and smooth muscle relaxation, The mechanism by which carbon monoxide activates soluble guanylyl cyclase (sGC) is similar to that of nitric oxide , and involves binding and dislocation of its heme-iron to induce a conformational change and activation of the catalytic site of guanylyl cyclase. Since researchers have proved the important role by nitric oxide and carbon monoxide in the pathogenesis of atherosclerosis. carbon monoxide has a much lower affinity for soluble guanylyl cyclase than nitric oxide. Decreased production or sensitivity to nitric oxide in atherosclerosis may be compensated for by an induction of heme oxygenase-1. The study on the correlation of endonenous carbon monooxide/heme oxygenase and nitrogen monoxide/nitricoxide synthase syesterm in atherosclerosis is unclear. The objective of the present study was to investigate the change rule of the correlation of endonenous carbon monooxide/heme oxygenase and nitrogen monoxide/nitricoxide synthase syesterm in atherosclerosis by RT-PCR, immunohistochemistry stain, biochemical analysis, electron microscopic technique, optical microscopic and so on. The main results were as follows:(1) Comparing with nomal control group ,the positive reaction of heme oxygenase -1 and the expression of heme oxygenase -1 mRNA both increased in the cholesterol goup, and the endogenous produced carbon monoxide increased with the reduction of area of diet-Induced atherosclerosis in rabbit (2) It was proved through immunohistochemistry stain that heme oxygenase-1 mostly distribute on the endothelial cells and smooth muscle cells of aorta. Comparing with the cholesterol goup, after putting in heme-L-lysinate, it would mostly increase the express of heme oxygenase-1mRNA and the concentration of endogenous produced carbon monoxide.After putting in ZnPP-â…¨, comparing with the cholesterol goup, it would inhibit the express of heme oxygenase-1mRNA and markedly reduce the concentration of endogenous produced carbon monoxide. Heme-L-lysinate have no effect on endogenous produced nitrogen monoxide and nitricoxide synthase activity, but ZnPP-â…¨ could markedly increase constructive nitricoxide synthase activity and endogenous produced nitrogen monoxide.(3) Comparing with the cholesterol goup, the L-Arginine group would mostly increase nitricoxide synthase activity and the concentration of endogenous produced nitrogen monoxide, and it had no effect on the express of heme oxygenase-1 mRNA and the concentration of endogenous produced carbon monoxide. After putting in L-NAME, comparing with the cholesterol goup, it would markedly inhibit nitricoxide synthase activity and the concentration of nitrogen monoxide, but it could mostly increase the express of heme oxygenase-1 mRNA constructive nitricoxide synthase activity and endogenous produced nitrogen monoxide.(4) Comparing with the cholesterol goup, the L-NAME group and ZnPP-â…¨ group could increase the express of c-myc mRNA and c-fos mRNA. The L-Arginine group and the heme-L-lysinate group could reduce the express of c-myc mRNA and c-fos mRNA.Conclusion: (1) It was proved that nitric oxide and carbon monoxide play the important role in the pathogenesis of atherosclerosis , and their affect do not the change of plasma levels of ox-LDL and total cholesterol. (2) Heme oxygenase-1 inhibits diet-Induced atherosclerosis in rabbit, though increasing the express of heme oxygenase-1 mRNA and the concentration of endogenous produced carbon monoxide.and regulating the express of c-myc mRNA and c-fos. mRNA. (3) The reciprocal correlation of heme oxygenase / carbon monooxide and nitricoxide synthase/nitrogen...