The Effect Of ENOS,MMP-1 And TIMP-1 In The Pathogenesis Of Pulmonary Hypertension Associated With Congenital Heart Disease

Objective: To investigate the effect of endothelial nitric oxide synthase (eNOS) , matrix metalloproteinase-l(MMP-l) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the pathogenesis of pulmonary hypertension associated with congenital heart disease.Methods: 60 patients with congenital heart disease who had left-to-right shunt were selected randomly and divided into 4 groups according to Heath-Edwards pulmonary vessel pathologic grading: group 0 (control group) was not PH(n=14), group I was grade I(n=18), group II was grade II (n=10) and groupIII was grade III(n=18). RT-PCR and immunohistochemical S-P were employed to detect the mRNA of cNOS, MMP-1 and TIMP-1 and the protein of eNOS, MMP-1, TIMP-1, collagen I and collagen III in the lung tissue of these patients.Results: (1) The contents of collagen I , III in lung tissue were significantly increased in group I , II, III compared with group 0 and group II , III compared with group I (P<0.01 or P<0.05).(2)The expression levels of MMP-1 mRNA, TIMP-1 mRNA and the expression level of protein of MMP-1 were distinctly raised in group I, II, III compared with group 0 (P<0.01 or P<0.05) and group II, III compared with group I (P<0.01 or P<0.05), the expression level of protein of TIMP-1 was distinctly raised in group HI compared with group 0, I and group II compared with group 0(P<0.01 or P<0.05), the ratio of TIMP-1/MMP-1 was significantly higher in group I , II, III, than in group 0(P<0.01 or P<0.05).(3)The expression levels of mRNA and protein of eNOS were significantly...