The Variation Of Serum MMP-9,TIMP-1 And VEGF In Patients With Congenital Heart Disease Complicating Pulmonary Hypertension

Objective To approach the level and variation of serum vascular endothelial growth factor(VEGF)and matrix metalloproteinase(MMP-9)metalloproteinase inhibition(TIMP-1)and assess the relation of them and the pulmonary hypertension(PH)in patients with congenital heart disease.Methods According to the preoperative pulmonary arterial systolic pressure(SPAP),81 patients with congenital heart disease of left-to-right shunt type were divided into four groups:no PH group(16 patients,SPAP＜30mmHg);light PH group: (21 patients,30 mmHg≤SPAP＜40mmHg),midrange PH(21 patient,40 mmHg≤SPAP＜70mmHg)and heavy PH(23 patient,SPAP≥70 mmHg). 19patients among the midrange PH and heavy PH group were comprehensively treated with PGE1 et al.24 patients of the total patients were operated.Before and after the treating or operating,the variation of these indexes would be also observed and examinated.The concentrations of serum MMP-9,TIMP-1 and VEGF were measured with ELISA.Then the ratio of MMP-9/TIMP-1 was calculated.A control group was made up of 21 unimpaired children.Results The concentrations of serum MMP-9,TIMP-1 and VEGF of 81 cases with congenital heart disease of left-to-right shunt type obviously increased(all P＜0.01).The level of MMP-9,TIMP-1 and VEGF in the groups of light PH, midrange PH and heavy PH were all increase with significant difference, compared with ones of control group(in light PH group and midrange PH group all MMP-9 P＜0.01,in heavy PH group MMP-9 P＜0.05,in heavy PH group TIMP-1 P＜0.01,in light PH group and midrange PH group TIMP-1 P＜0.05, midrange PH group VEGF P＜0.01,light PH group and heavy PH group P＜0.05).However,in no PH group,VEGF was the only index which was significantly increased compared with it in control group.There were also significant difference in the ratios of MMP-9/TIMP-1 between midrange PH group and control group.While there was not obvious change in the ratios of MMP-9/TIMP-1 in the no PH group,light PH and the heavy group.After PGE1 had been applied to treat 19 patients for fourteen days,The levels of serum MMP-9,TIMP-1 and VEGF were all obviously lower than them before being treated(all P＜0.01)Similarly,the concentrations of serum MMP-9,TIMP-1, VEGF and MMP-9/TIMP-lin 24 patients were also significantly decreased compared with those before being operated(the three of former P＜0.01,the latter P＜0.05).The relationships all of them,MMP-9 and VEGF,MMP-9 and MMP-9/TIMP-1,MMP-9 and TIMP-1 in congenital heart disease with pulmonary hypertension are right ones,While TIMP-1 and MMP-9/TIMP-1 have a negative relationship.Conclusions(1)The concentrations of serum VEGF,MMP-9,TIMP-1 in patients with congenital heart disease of left-to-right shunt type increase with different degrees.Especially,such variations are accompanied with the obvious changes of MMP-9/TIMP-1 during the stage of midrange PH.They may synergistically contribute to pulmonary vascular reconstitution.(2)The levels of serum VEGF,MMP-9 and TIMP-lcan be degraded obviously after patients have be treated with PGE1 for fourteen days, which may be one of the mechanisms that PGE1 can reverse pulmonary vascular remodeling.(3)The levels of serum VEGF,MMP-9 and TIMP-1 can also be degraded obviously after seven days of patients' operations.Its mechanism probably be such operations disrupting the abnormal hemodynamics of congenital heart disease.The abnormal hemodynamics is the initial factor that cause pulmonary vascular remodeling.