Inflammatory Mechanisms Of Atherosclerosis Induced By Homcyteinemia

Parti Folic Acid Reduced Chemokines MCP-1 And IL-8 ReleaseFrom Rats With HyperhomocysteinemiaObjective To investigate effects of supplementation of folic acid on the release of Chemokines MCP-1 and IL-8 in the Rats With Hyperhomocysteinemia induced by ingestion of execess methionine(Met).Methods Thirty male SD rats were randomly divided into 3 groups(n=10 for each group): control group(Control), high homocysteinemia group (Hhcy) and folate treatment group (FA). They were fed with nomal diet, normal diet enriched by 1.7% Met and nomal diet plus 1.7% Met and 0.006% folate for 45 days. The levels of total plasma homocysteine(thcy) in the three groups were mesured. Respectively, the concentration of Chemokines MCP-1 in plasma and release from peripheral blood mononuclear cells (PBMCs) were detected by enzyme immunoassays. Results (1). A high methionine diet for 45 days is sufficient to induce hyperhomocysteinemia. Folate supplementation to the rats fed with the high-methenine diet prevented an elevation of Hcy levels in the blood(P<0.01). (2). Compared with control groups, hyperhomocysteine groups had elevated plasma levels of chemokines MCP-1 in plasma and in PBMCs stimulated by ox-LDL(P<0.05; P<0.01). CXC chemokine IL-8 released from PBMCs also increased in this group(P<0.05) and the levels in plasma had no significant difference(P>0.05). (3). During folic acid treatment, normalization of homocysteine levels was accompanied by a marked reduction of MCP-1 in plasma and in PBMCs simulated by ox-LDL(P<0.05; P<0.01). IL-8 released from PBMCs also decresed(P<0.05) and the levels in plasma had no significant difference(P>0.05). Conclusion Hyperhomocysteinemia had elevated circulating levels of CC chemokine MCP-1 in plasma and increased oxidized low density lipoprotein-induced release of the CC chemokine MCP-1 and CXC chemokine IL-8 from peripheral blood momonuclear cells. During folic acid treatment, normalization of homocysteine levels was accompanied by a marked reduction in oxidized low density lipoprotein-stimulated release of CC chemokine MCP-1 and CXC chemokine IL-8 in peripheral blood momonuclear cells from Hhcy groups. Homocysteine-mediated inflammatory process in vessal wall and formation of atherosclerosis in early stage can be suppressed by folate. Part II Folic Acid Reduces Cytokines Monocyet Chemoattractant protein-1 And Adhesion Molecules VCAM-1 Expession In Aortic OfRats With HyperhomocysteinemiaObjective To investigate effects of supplementation of folic acid on the exprssion of MCP-1 and VCAM-1 in aortic of Rats With Hyperhomocysteinemia induced by ingestion of execess methionine(Met).Method Thirty male SD rats were randomly divided into 3 groups(n=10 for each group): control group(Control), high homocysteinemia group (Hhcy) and folate treatment group (FA). They were fed with nomal diet,normal diet enriched by 1.7% Met and nomal diet plus 1.7% Met and 0.006% folate for 45 days. The levels of total plasma homocysteine(thcy) in the 3 groups were mesured. Respectively, the expression of MCP-1 and VCAM-1 protein on aortic of rats were detected by immunohistochemistry and western-blot; MCP-1 and VCAM-1 mRNA levels were detected by semi-quantantive RT-PCR.Results The high-methionine diet resulted in a significant increase in the plasma Hcy levels in control rats (140.68 ± 36.87μmmol/L versus 6.47±1.10μmmol/L, P<0.01). Serum Hcy levels were significantly lower in rats fed with high-methionine plus folate-rich diet than in rats fed with the high-methionine diet(50.58 ±21.84 μmmol/L versus 140.68± 36.87μmmol/L, P<0.01); The expression of MCP-1 and VCAM-1 at protein and mRNA levels is higher in aortic of rats fed with the high-methionine die than those in control rats, the expression of MCP-1 and VCAM-1 at protein and mRNA levels was significantly reduced in aortic of rats fed with high-methionine plus folate-rich diet compared with rats fed with high-methionine diet.Conclusion A high methionine diet for 45 days is sufficient to induce hyperhomocysteinemia. folate supplementation to the rats fed the high-methenine diet prevented an elevation of Hcy levels in the blood, on the onther hand, it reduces the expression of MCP-1 and VCAM-1 in aortic of rats with hyperhomocysteinemia.