Affection Of Vascular Endothelial Growth Factor On The Expression Of ADAMTS5、 ADAMTS4、MMP9in Human Umbilical Veins Endothelia Cells

Background and ObjectiveCoronary heart disease is a serious threat to human health.Acute coronary syndromes（ACS） are most frequently caused by acute disruption of an vulnerable plaque,platelet aggregation and thrombosis. Plaque rupture is the most frequent cause of thrombosis. The excessive degradation of the extracellular matrix（ECM） scaffold has been implicated as one of the major molecular mechanisms in the process. Recent studies suggest that proteinases such as MMP9, ADAMTS4may be as very important biomarkers in recognizing patients with ACS. These proteinases may promote destabilization and complication of atherosclerotic plaques by degrading extracellular matrix collagen of overlying cap. VEGF possesses the most effective specificity in promoting angiogenesis. Recent clinical trials indicate that evident expression of VEGF in unstable plaques, and show significantly relevant with the severity of ACS.To investigate the expression of ADAMTS5、 ADAMTS4and MMP9in Human umbilical veins endothelia cells（HUVEC） after stimulated by different concentration of rhVEGF₁₆₅ and to investigate the mechanism of VEGF on the instable plaques.Methods1.HUVEC were cultured and stimulated by different concentration of rhVEGF₁₆₅（Ong/ml, lOng/ml,20ng/ml,50ng/ml）for24h.2. Real Time PCR was used to detect the mRNA expression of ADAMTS5、 ADAMTS4 and MMP9respectively.3.Western blot was applied to examine ADAMTS5、 ADAMTS4、 MMP9protein levels respectively.Resultsl.The results indicated that the mRNA expression of ADAMTS5、 ADAMTS4and MMP9in rhVEGF₁₆₅10ng/ml groups were:1.161±0.029,1.238±0.077,1.357±0.059, the control groups are1±0, P<0.05.In rhVEGF₁₆₅20ng/ml groups were:2.298±0.092,2.501±0.009,2.637±0.047, P<0.05.In rhVEGF₁₆₅50ng/ml groups were:2.517±0.019,2.736±0.08,3.21±0.079, P<0.05.The mRNA expression of ADAMTS5. ADAMTS4, MMP9display a dose-dependent manner, r=0.873,0.874,0.925, P<0.01.2.Compared with the control groups, the protein expression of ADAMTS5, ADAMTS4and MMP9in rhVEGF₁₆₅ lOng/ml groups were:0.091±0.006vs0.043±0.005,0.147±0.003vs0.047±0.005,0.172±0.029vs0.086±0.009, P<0.05.In rhVEGF,6520ng/ml groups were:0.1457±0.007vs0.043±0.005,0.39±0.007vs0.047±0.005,0.525±0.085vs0.086±0.009, P<0.05.In rhVEGF₁₆₅50ng/ml groups were:0.1767±0.003vs0.043±0.005,0.624±0.055vs0.047±0.005,0.598±0.024vs0.086±0.009, P<0.05. the protein expression of ADAMTS5, ADAMTS4, MMP9display a dose-dependent manner, r=0.9910.970,0.946, P<0.01.Conclusion1.VEGF may play an important role in the occurrence and developmence of atherosclerosis by up regulating the expression of ADAMTS5. ADAMTS4and MMP9.2. VEGF can promote the process of arteriosclerosis, can be regarded as an important predictor of plaque stability.