Role of serum MMP-2, TIMP-1 and VEGF in pulmonary vascular reconstitution in patients with congenital heart disease

AIM: To investigate the roles of serum matrix metalloproteinase-2 (MMP-2), metalloproteinase inhibition-1 (TIMP-1) and vascular endothelial growth factor (VEGF) in pulmonary vascular reconstitution 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 pulmonary hypertension (PH) group (n=16, SPAP<4.00 kPa), mild PH group (n=21, 4.00 kPa≤SPAP<5.33 kPa), medium PH group (n=21, 5.33 kPa≤SPAP<9.33 kPa) and severe PH (n=23, SPAP≥9.33 kPa). Twenty one healthy children undergoing routine physical examination were included as the control group. Of the 84 patients, 19 were comprehensively treated with PGE1 and 24 were treated surgically. Concentrations of serum MMP-2, TIMP-1 and VEGF were measured with ELISA and the ratio of MMP-2/TIMP-1 was calculated. RESULTS: Compared with those of the control group, concentrations of serum MMP-2 and VEGF obviously increased in all four groups and the levels of TIMP-1 significantly increased in mild, medium and severe groups. The ratio of MMP-2/TIMP-1 also significantly increased in no PH, mild PH and medium PH groups. After treatment with PGE1 for 14 days, the levels of serum MMP-2, TIMP-1 and VEGF all obviously decreased. Surgical intervention also significantly decreased the levels of MMP-2, TIMP-1, MMP-2/TIMP-1 and VEGF. CONCLUSION: Serum VEGF and MMP-2 may synergistically contribute to pulmonary vascular reconstitution in patients with congenital heart disease of left-to-right shunt type. PGE1 significantly decreases the levels of serum MMP-2, TIMP-1 and VEGF, which may show how PGE1 is involved in reversing pulmonary vascular remodeling. Levels of serum VEGF, MMP-2, MMP-2/TIMP-1 and TIMP-1 decrease significantly 7 days postoperatively.