Changes Of Serum Matrix Metalloproteinase-2 And Tissue Inhibitor Metalloproteinase-2 In Patients With Congenital Heart Disease Complicating Pulmonary Hypertension

Objectives:To explore the levels and variation of serum matrix metalloproteinase- 2 (MMP- 2) and tissue inhibitor Metalloproteinase -2 (TIMP-2) in patients with congenital heart disease(CHD) complicating pulmonary hypertension (PH) and to understand their relationship.Methods:According to the preoperative pulmonary arterial systolic pressure (SPAP),40 patients with CHD were divided into 4 groups: no PH group (11 cases, SPAP < 4 kPa), light PH group (11 cases, 4. 0 kPa≤SPAP<5. 33 kPa), moderate PH group (11 cases, 5. 33 kPa≤SPAP<9.33 kPa) and heavy PH group (7 patients, SPAP≥9.33 kPa) . The concentrations of serum MMP-2 and TIMP-2 were measured with enzyme-linked imunosorbent assay(ELISA).Then the rate of MMP-2/TIMP-2 was calculated.Results:①The concentrations of serum MMP-2 increased remarkably in CHD groups, compared with control group (P<0.01).②And the level of TIMP-2 was also significantly advanced in all groups with PH. The rates of MMP-2/TIMP-2 in the no PH group, light PH and moderate PH group obviously increased (P<0.01).But there were not obvious changes of the rate of MMP-2/TIMP-2 whether in the heavy PH group or control group(P>0.05).③There were positive relationships between MMP-2 and TIMP-2,MMP-2 and MMP-2/TIMP-2. However, there was negative relationship between TIMP-2 and MMP-2/TIMP-2(P<0.01).④there were not obvious changes of the level of MMP-2 and TIMP-2 whether in pulmonary artery or in inferior caval vein (P>0.05).Conclusions:During the progression of PH in cases of CHD, MMP-2 and TIMP-2 may play an important role in the development of PH.1. The concentrations of serum MMP- 2 in patients with CHD of left-to-right shunt type obviously increased. So MMP-2 may synergistically contribute to pulmonary vascular reconstitution in whole process. It may play an important role in migration and reproduction of smooth muscle cells in the early stage of PH.2. TIMP-2 could decrease the breakdown of matrix collagen and reduce inflammatory reaction, and it might have a beneficial effect on pulmonary hypertension. It is related to the formation of vascular remodeling in the middle and late stage of PH.3. MMP-2 and TIMP-2 correlated with PH severity, and their secretion imbalance might lead to prolongation of the disease course.