|Budget Amount *help
¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1998 : ¥1,200,000 (Direct Cost : ¥1,200,000)
The molecular mechanism involved in pulmonary vascular disease (PVD) associated with congenital heart disease (CHD) remains uncertain. Evidence suggesting that angiotensin converting enzyme plays an important role in pulmonary vascular pathology led us to hypothesize that mast cell chymase, another angiotensin I converting enzyme, also had the potential to contribute to the development of PVD in CHD.Twenty-three patients ranging from age 3 months to 45 years with atrial or ventricular or both septal defects with increased pulmonary arterial blood flow and pressure, with pulmonary vascular resistance ranging from 1.3 to 8.1 unit m^2, were studied. Mast cells and mast cell chymase were immunohistochemically identified in the lung biopsy tissues obtained during corrective surgery. There was a significant difference in numbers of total mast cells between patients (n=23) and controls (n=10) with normal pulmonary circulation (p<0.01). Moreover, chymase-containing mast cells in the lung tissues of CHD patients showed striking differences from those of controls. In the patients, 72% of lung mast cells contained chymase, compared to only 15% in controls (p<0.000l). Chymase-containing mast cells predominantly appeared in the media and adventitia of vessel walls. Importantly, angiotensin II was immunohistochemically detected in perivascular lesions where chymase was present, but not in the lesions where chymase was sparsely seen. Furthermore, the number of chymase-containing mast cells was correlated with pulmonary vascular resistance (r=0.64). These findings suggest a possible role of mast cell chymase in the development of early-stage PVD in CHD patients.