Background: The exact mechanism of spontaneous closure of perimembranous ventricular septal defect (PMVSD) is still unknown. We hypothesized that valvular interstitial cells (VICs) mediate extracellular matrix remolding and migration in the aneurysms of membranous septum by secretion of serine proteinase and its inhibitor.
Methods: The functional characteristics of VICs in 15 aneurysms and in 4 normal tricuspid septal leaflets at autopsy were evaluated by detecting the expression of uPA, PAI-1, and SMA-α in the specimen using immunohistochemical method.
Results: uPA and SMA-α were recognized predominantly in VICs which located mainly in regions adjacent to the endothelium and smooth muscle cells of blood vessels. PAI-1 was found in both VICs which located mainly in granulation tissue and endothelial cells..Two types of granulation tissue (myxoid and fibrous tissue) were associated with the aneurysms. Nine aneurysms expressed high uPA activity and low PAI-1 activity and uPA / PAI-1 ratio was 1.78; while the other 6 cases expressed low uPA activity and high PAI-1 activity and uPA / PAI-1 ratio was 0.14, suggesting different ability to close the septum in patients with PMVSD..
Conclusion: Expression of uPA, PAI-1 and SMA-α in VICs suggests that interactions among these molecules contribut to extracellular matrix remolding and cell migration during the aneurysmal formation and development. Altered expression of uPA and PAI-1 reactivity and different uPA / PAI-1 ratio may be involved in the different abilities to close the septum in patients with PMVSD.