1. Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
2. Division of Cardiology, Department of Pediatrics, Mackay Memorial Hospital, Hsinchu, Taiwan
3. Division of Chest Medicine, Department of Internal Medicine, Mackay Memorial Hospital, Hsinchu, Taiwan
4. Division of Cardiology, Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
† Equal contribution as the first author
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