Objective: To study the expression and pathological implication of transforming growth factor-1 (TGF-1) and endothelin-1 (ET-1) in intraacinar pulmonary arterioles of children with congenital heart disease and pulmonary hypertension (HP).
Methods: Forty-one children with left-to-right shunt congenital heart disease were studied including 25 cases of HP (group A), 16 cases without HP (group B) and 10 children without congenital heart disease as the contols (group C). Expression of TGF-beta1 mRNA and ET-1 mRNA in intraacinar pulmonary arteriolar (IAPA) was studied using in-situ hybridization and image pattern analysis of their absorption values (A value). Changes of the intraacinar arterioles and lung tissue were studied by elastic fiber staining and electronic microscopy respectively.
Results: (1) There was a significant difference in the amount of intraacinar pulmonary arterioles (partial-muscular and muscular) counted in either group A or B in comparing with that of group C (F values 149.96 and 142.01 respectively, P < 0.01); (2) Electronic microscopy demonstrated endothelial proliferation of the small arteries, thickening of arteriolar wall, increased density of collagen fibers at adventitia and increased thickness of the capillary basal membrane; (3) The A value of TGF-beta1 mRNA expressed in the pulmonary arterioles of groups A and B by in-situ hybridization were 0.1988 +/- 0.0498 and 0.1098 +/- 0.0428 respectively, however, the expression was weak in group C (A value: 0.0578 +/- 0.0096). There were all significant between each two groups (F = 45.95, P < 0.01). The expression of ET-1 mRNA was markedly increased as well in the endothelial cells of pulmonary arterioles in both groups A and B, with A values of 0.1692 +/- 0.0205 and 0.1004 +/- 0.0140 respectively, whereas the expression was weak in group C (A value of 0.0746 +/- 0.0119). There were all significant between each two groups (F = 139.996, P < 0.01).
Conclusions: The number of intraacinar pulmonary partial-muscular and muscular arterioles in patients with left-to-right shunt congenital heart defect is drastically increased, along with marked restructuring of the pulmonary vasculatures. In addition, there seems a correlation present between the overexpression of TGF-beta1 mRNA and ET-1 mRNA in intraacinar pulmonary arterioles and the occurrence of pulmonary hypertension in patients with congenital heart disease.