Immunohistochemical detection of uPA, PAI-1, and alpha-SMA in aneurysms of patients with perimembranous ventricular septal defect.
OBJECTIVE
A perimembranous ventricular septal defect (PMVSD) may be partially or completely occluded by aneurysms that originate from the tricuspid valve leaflets, though the exact mechanisms of closure remain unknown. It is hypothesized that valvar interstitial cells (VICs) mediate extracellular matrix (ECM) remodeling in aneurysms via the secretion of a serine proteinase and its inhibitor.


METHODS
The functional characteristics of VICs in 15 aneurysms and in four normal tricuspid valve leaflets obtained at autopsy were evaluated by detecting the expression of urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and alpha-smooth muscle actin (alpha-SMA) in the specimens, using immunohistochemical methods.


RESULTS
uPA and alpha-SMA were recognized predominantly in VICs located mainly in regions adjacent to the endothelium and smooth muscle cells of blood vessels. PAI-1 was identified in VICs found mainly in granulation tissues, and in endothelial cells. Two types of granulation tissue (myxoid and fibrous tissue) were associated with aneurysms. Nine aneurysms expressed a high uPA activity and a low PAI-1 activity (uPA/PAI-1 ratio 1.78), while six aneurysms expressed a low uPA activity and a high PAI-1 activity (uPA/PAI-1 ratio 0.14).


CONCLUSIONS
The expression of uPA, PAI-1 and alpha-SMA in VICs suggests that interactions among these molecules contribute to ECM remodeling during aneurysm formation and development. This provides a potential mechanism for defect closure in patients with PMVSD.
Pediatric Intensive Care Unit, Shanghai Children's Medical Center, Shanghai Jiaotong University, Shanghai, PR China.
Juan
J
Qian
Kun
K
Sun
Ping
P
Shen
Min-Zhi
MZ
Yin
D000199:Actins / Q000378:metabolism*; D003239:Connective Tissue Cells / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D006322:Heart Aneurysm / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006345:Heart Septal Defects, Ventricular / Q000150:complications / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D057057:Serine Proteases / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
C541116:ACTA2 protein, human; D000199:Actins; D019394:Ki-67 Antigen; D017395:Plasminogen Activator Inhibitor 1; D057057:Serine Proteases; D014568:Urokinase-Type Plasminogen Activator