Effect Of Homocysteine On Expression Of Matrix Metalloproteinase In Human Vascular Endothelial Cell

Objective: To investigate the mechanism of artherosclerosis and plaque disruptioninduced by disfunction of vascular endothelial cell with hyperhomocysteinaemia , we observe the effects of homocysteine on the genetic expression of matrix metalloproteinases(MMPs) in human vascular endothelial cell in 1, 6, 24 hours.Method: To incubate HUVEC CRL-1730(human umbilical vein vascular endothelia cell) in vitro with difference concentration (0, 10,50, 100, 1000μmol/L) of homocysteine, then collecte cells in 1,6 and 24 hours after incubation. To semiquantitative the mRNA expression of MMP-1,MMP-9 and TIMP-1 (tissue inhibitors of metalloproteinases -1)by RT-PCR(reverse transcription- polymerase chain reaction) method.Result:(1)The HUVEC CRL-1730 express MMP-1,MMP-9 and TIMP-1 m RNA Without homocysteine and existed physiological concentration homocysteine. Compare with 1 hour, the expression of MMP-1 and proportionality of MMP-1 and TIMP-1 significantly depressed in 6,24 hours(p<0.05). It is indiscrimination of the expression of MMP-1 and proportionality of MMP-1 and TIMP-1 in 6,24 hours(p>0.05). Compare with 1 hour, the expression of MMP-9 and proportionality of MMP-9 and TIMP-1 significantly up-regulated in 6,24 hours(p<0.05). It is indiscrimination of the expression of MMP-1 and proportionality of MMP-1 and TIMP-1 in 6,24 hours(p>0.05).The expression of TIMP-1 was indiscrimination(p>0.05).(2). Homocysteine of pathology concentration (50-1000μmol/L) increased the expression of MMP-1 and proportionality of MMP-1 and TIMP-1, MMP-9 and TIMP-1 significantly in a dose-depended manner(p<0.05) . Homocysteine(50-100umol/L) increased the expression of MMP-9 and reduced the the expression of MMP-9 at a high level(1000umol/L). The expression of TIMP-1 was down regulation by pathology concentration homocysteine in a dose-depended manner(p<0.05).Conclusion: (1)MMP-1,MMP-9,TIMP-1 expression were constructive in HUVEC CRL-1730 . The express level and the proportionality of MMP-land TIMP-1, MMP-9and TIMP-1 achieved and maintained in equilibrium states. In physiological condition, VEC expressed MMPs and TIMP-1 to regulated the extracellular matrix metabolism and keeped its dynamic balance.(2) Pathology concentration homocysteine change the expression of MMP-1,MMP9 and TIMP-1 in vascular endothelial celland further up-regulated the expression of MMP-1 and the proportionality of MMP-1 and TIMP-1, MMP-9 and TIMP-1 in a dose dose-depended manner. So homocysteine effects on the genetic expression of matrix metalloproteinases(MMPs) in human vascular endothelial cell and then promoted extracellular matrix degradation,induced plaque disruptive.