Birth associated changes in pulmonary arterial connective tissue gene expression in the normal and hypertensive lung

Objectives: To determine the temporal and spatial expression of the connective tissue precursors, procollagen and tropoelastin mRNA in normal and pulmonary hypertensive porcine pulmonary arteries from birth onwards. Methods: Using in situ hybridisation, connective tissue gene expression for procollagen alpha 1(I) and alpha 1(III) and tropoelastin was studied in intrapulmonary arteries from normal piglets, 5 min-16 weeks, and from piglets made pulmonary hypertensive by exposure to hypobaric hypoxia for 3 days, from birth, 3 or 14 days of age. In addition, Type III pN-procollagen, tropoelastin and collagen I and III were studied by immunohistochemistry. Quantitative or semi-quantitative techniques were applied to both in situ and immunohistochemical studies. Results: Procollagen alpha 1(I) and alpha 1(III) mRNA expression increased rapidly in the media and adventitia between birth and 3 days of age (P<0.05). The increase was transient and the number of cells expressing procollagen mRNA decreased to the low newborn number after 6 days of age. Type III pN-procollagen immunostaining was greatest in newborn elastic and muscular arteries and then decreased. Collagen I and III increased mainly after 6 days of age. In animals exposed to chronic hypobaric hypoxia from birth, the increase in procollagens I and III mRNA was prevented. Exposure to hypoxia from 3 or 14 days led to little change in either gene expression or in procollagen and mature collagen from the normal. Tropoelastin gene expression was high at birth in the endothelium and media for the first 6 days, and then decreased. Normally, tropoelastin decreased in the media and increased in the adventitia after 16 days of age. Hypoxia had no effect on the mRNA but led to increased tropoelastin. Conclusion: We demonstrated marked, rapid changes in temporal and cell specific connective tissue gene expression in normal pulmonary arteries immediately after birth as the vasculature remodels. Each gene appeared to have its own timetable of expression and responded differently to hypoxia-induced hypertension (C) 2000 Elsevier Science B.V. All rights reserved.