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 connect ive tissue precursors, procollagen and tropoelastin mRNA in normal and pulm onary hypertensive porcine pulmonary arteries from birth onwards. Methods: Using in situ hybridisation, connective tissue gene expression for procolla gen alpha 1(I) and alpha 1(III) and tropoelastin was studied in intrapulmon ary arteries from normal piglets, 5 min-16 weeks, and from piglets made pul monary hypertensive by exposure to hypobaric hypoxia for 3 days, from birth , 3 or 14 days of age. In addition, Type III pN-procollagen, tropoelastin a nd collagen I and III were studied by immunohistochemistry. Quantitative or semi-quantitative techniques were applied to both in situ and immunohistoc hemical studies. Results: Procollagen alpha 1(I) and alpha 1(III) mRNA expr ession increased rapidly in the media and adventitia between birth and 3 da ys of age (P<0.05). The increase was transient and the number of cells expr essing procollagen mRNA decreased to the low newborn number after 6 days of age. Type III pN-procollagen immunostaining was greatest in newborn elasti c and muscular arteries and then decreased. Collagen I and III increased ma inly after 6 days of age. In animals exposed to chronic hypobaric hypoxia f rom birth, the increase in procollagens I and III mRNA was prevented. Expos ure to hypoxia from 3 or 14 days led to little change in either gene expres sion or in procollagen and mature collagen from the normal. Tropoelastin ge ne expression was high at birth in the endothelium and media for the first 6 days, and then decreased. Normally, tropoelastin decreased in the media a nd 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 vasc ulature remodels. Each gene appeared to have its own timetable of expressio n and responded differently to hypoxia-induced hypertension (C) 2000 Elsevi er Science B.V. All rights reserved.