Increased expression of mast cell chymase in the lungs of patients with congenital heart disease associated with early pulmonary vascular disease

The molecular mechanism involved in pulmonary vascular disease (PVD) associ ated with congenital heart disease (CHD) remains uncertain. Evidence sugges ting that angiotensin converting enzyme plays an important role in pulmonar y vascular pathology led us to hypothesize that mast cell chymase, another angiotensin I converting enzyme, also had the potential to contribute to th e development of PVD in CHD. Twenty-three patients 3 mo to 45 yr of age wit h atrial or ventricular or both septal defects with increased pulmonary art erial blood flow and pressure, with pulmonary vascular resistance ranging f rom 1.3 to 8.1 units/m(2), were studied. Mast cells and mast cell chymase w ere immunohistochemically identified in the lung biopsy tissues obtained du ring corrective surgery. There was a significant difference in numbers of t otal mast cells between patients (n = 23) and control subjects (n = 10) wit h normal pulmonary circulation (p < 0.01). Moreover, chymase-containing mas t cells in the lung tissues of patients with CHD showed striking difference s from those of control subjects. In the patients, 72% of lung mast cells c ontained chymase, compared with only 15% in control subjects (p < 0.0001). Chymase-containing mast cells predominantly appeared in the media and adven titia of vessel walls. Importantly, angiotensin II was immunohistochemicall y detected in perivascular lesions where chymase was present, but not in th e lesions where chymase was sparsely seen. Furthermore, the number of chyma se-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 patients with CHD.