Circulating matrix metalloproteinase-2 and -9 enzyme activities in the children with ventricular septal defect

Abstract

Ventricular septal defect (VSD) is the most common form of congenital heart diseases. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases involved in causal cardiac tissue remodeling. We studied the changes of circulating MMP-2 and MMP-9 activities in the patients with VSD severity and closure. There were 96 children with perimembranous VSD enrolled in this study. We assigned the patients into three groups according to the ratio of VSD diameter/diameter of aortic root (Ao). They were classified as below: Trivial (VSD/Ao ratio ≤ 0.2), Small (0.2 < VSD/Ao ≤ 0.3) and Median (0.3 < VSD/Ao) group. Plasma MMP-2 and MMP-9 activities were assayed by gelatin zymography. There was a significant higher MMP-2 activity in the VSD (Trivial, Small and Median) groups compared with that in Control group. The plasma MMP-9 activity showed a similar trend as the findings in MMP-2 activity. After one year follow-up, a significant difference in the MMP-9 activity was found between VSD spontaneous closure and non-closure groups. In conclusion, a positive trend between the severity of VSD and activities of MMP-2 and MMP-9 was found. Our data imply that MMP-2 and MMP-9 activities may play a role in the pathogenesis of VSD.

Keywords: Matrix metalloproteinase-2; Matrix metalloproteinase-9; Tissue inhibitor of metalloproteinase-3; Ventricular septal defect.

Figure 1

The circulating MMP-2 and MMP-9 activities in the patients with different levels of VSD severity. The MMP-2 (A) and MMP-9 (B) activities in the patients with different VSD severity were determined by gelatin zymography. The gelatinase activities detected in this study were based on pro-MMP-2 (72 kDa) or pro-MMP-9 (95 kDa). Each symbol represents one individual, and horizontal bars represent mean value in each group. The compared results of the MMP-2 or MMP-9 activity in the Control (n = 12), Trivial (n = 47), Small (n = 30) and Median (n = 19) groups with one way ANOVA analysis were performed. ** indicates p < 0.01, compared to the Control group.

Figure 2

Correlations between circulating MMPs activities and VSD size or VSD/Ao ratio in the children patients. Pearson's correlation analysis (SPSS statistics package, Chicago, IL, USA) was applied. Plasma MMP-2 activity in the VSD patients was insignificantly correlated with the VSD size (A) and VSD/Ao (B). Whereas, MMP-9 activity was significantly and positively correlated with the VSD defects size (C) and VSD/Ao (D) (p < 0.05).

Figure 3

Circulating MMPs activities in the patients who received serial echocardiographic follow-up examinations. The MMP-2 (A) and MMP-9 (B) activities in the plasma from each VSD closure and non-closure patient were indicated, with horizontal bars representing mean values in each group. ** indicates p < 0.01.