Active collagen synthesis by pulmonary arteries in pulmonary hypertension complicated by congenital diaphragmatic hernia.

The high mortality rate for patients with congenital diaphragmatic hernia (CDH) has been attributed to pulmonary hypoplasia and persistent pulmonary hypertension (PPH). The factors that cause vasoconstriction and vascular remodeling in PPH are not fully understood. Immunohistochemistry was performed on lung tissue obtained from postmortem CDH patients with pulmonary hypoplasia and PPH (n = 21) using the following antibodies: alpha smooth muscle-actin (ASMA), transforming growth factor-beta (TGF-beta), isoform specific (TGF-beta 1, -beta 2, -beta 3), and M-57. Normal lung tissues from age-matched sudden infant death syndrome patients (SIDS, n = 8) were obtained as controls. TGF-beta 3 immunoreactivity was observed in the adventitia but not in the media of pulmonary muscular arteries in patients with CDH. TGF-beta 1, -beta 2 immunoreactivity was either absent or faintly expressed in pulmonary arteries in CDH patients. No TGF-beta staining was observed in the pulmonary vasculature of SIDS patients. Newly synthesized procollagen (M-57) was easily detected in the media and adventitia in a large number of pulmonary arteries in all patients with CDH and in the neointima in two patients with long standing PPH. No M-57 staining was seen in the media of pulmonary arteries of the lungs of SIDS patients. These observations suggest a potential role of TGF-beta 3 but not TGF beta 1 or TGF beta 2 in pulmonary vascular remodeling and that smooth muscle cells in muscular pulmonary arteries are actively synthesizing collagen in patients with CDH complicated by PPH.