Role of mast Cell chymase in the development of pulmonary hypertension associated with congenital heart diseases

先天性心脏病(CHD)合并肺血管疾病(PVD)的分子机制尚不清楚。血管紧张素转换酶在肺血管病理中起重要作用的证据使我们推测，肥大细胞糜酶，另一种血管紧张素转换酶，也有可能在冠心病的PVD的发生发展中起作用。23例年龄3个月至45岁的房间隔或房间隔缺损合并肺动脉血流和压力增加的患者，肺血管阻力在1.3~8.1单位m^2之间。采用免疫组织化学方法检测矫正术中肺活检组织中肥大细胞和肥大细胞糜酶的表达。肺循环正常的患者(n=23)和对照组(n=10)的肥大细胞总数差异有统计学意义(p&lt；0.01)。此外，冠心病组肺组织中含有乳糜酶的肥大细胞与对照组相比有显著差异。在患者中，72%的肺肥大细胞含有凝乳酶，而对照组只有15%(p&lt；0.000l)。含有糜酶的肥大细胞主要分布在管壁的中膜和外膜。重要的是，血管紧张素II在有糜酶存在的血管周围病变中被检测到，但在糜酶稀少的病变中没有检测到。此外，含糜酶的肥大细胞数量与肺血管阻力呈正相关(r=0.64)。这些发现提示肥大细胞糜酶可能在CHD患者早期PVD的发生发展中起作用。

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.