Expression Of MMP-9 And TIMP-1 In Hyperhomocysteinemic Rats

Objective:To observe expression of matrix metalloproteinases-9(MMP-9) and tissue inhibitors of metalloproteinases-1 (TIMP-1) in hyperhomocysteinemic rats, to observe effects of supplementation of folate,vitamin-B12 (VitB12) on the hyperhomocysteinemia(HHcy) and atherosclerosis(As) induced by ingestion of excess methionine, and to investigate the mechanism of As induced by HHcy.Methods:Thirty male Wistar rats were randomly divided into 3 groups:control group which was fed with normal diet;methionine group,which was fed with normal diet plus 2%methionine;and intervention group, which was fed with normal diet plus 2%methionine and 0.5mg folate,25ug VitB12 as daily supplementation for 8 weeks. Serum levels of homocysteine(Hcy), MMP-9, TIMP-1 were assessed. The pathological change of carotid artery was observed.Results:(1)Compared with control group the level of Hcy (11.63±4.36 umol/L),was significantly higher in intervention group (16.21±4.41umol/L) and methionine group (20.57±4.34umol/L),P<0.05.Compared with intervention group the level of Hcy was significantly higher in methionine group,P<0.05. (2)Compared with control group the level of MMP-9 (4.63±0.82ng/ml) was significantly higher in intervention group (5.72±0.68 ng/ml) and methionine group (6.59±1.04 ng/ml), P<0.05. Compared with intervention group the level of MMP-9 was significantly higher in methionine group,P<0.05.(3)Compared with control group the level of TIMP-1 (1179.53±243.76pg/ml) was significantly higher in intervention group (1438.83±185.63 pg/ml) and methionine group (1640.73±184.40 pg/ml),P<0.05. Compared with intervention group the level of TIMP-1 was significantly higher in methionine group,P<0.05.(4)The level of Hcy has direct correlation whith level of MMP-9 in control group (r=0.825, P< 0.01), intervention group(r=0.963,P< 0.01) and methionine group(r=0.860, P< 0.01). The level of Hcy has direct correlation whith level of TIMP-1 in intervention group (r=0.950, P< 0.01) and methionine group(r=0.547, P< 0.01),but in control group(r=0.255, P> 0.05) the level of Hcy has noncorrelation whith level of TIMP-1.(5) There were hyperplasia and derangement of smooth muscle, syzygium of elastic fibers on aortic tunica media in methionine group.Compared with control group, there were no differences of vessel wall in intervention group.Conclusion:HHcy induces extracellular matrix (ECM) degradation and vessel wall remodeling by increasing expression of MMP-9 and TIMP-l,which may be one of the pathogenesies of atherosclerosis.VitB12 and folate supplementation can prevent HHcy,and the occurrence of As.