TENASCIN SYNTHESIS, DEPOSITION, AND ISOFORMS IN MONOCROTALINE-INDUCEDPULMONARY HYPERTENSIVE RAT LUNGS

Monocrotaline (MCT)-induced pulmonary hypertension is characterized by alterations in vascular extracellular matrix and neomuscularization o f small blood vessels. Tenascin (TN) is a matrix glycoprotein which mo dulates cellular attachment, proliferation, and migration. The present study used immunohistochemistry and Northern analyses to examine the hypothesis that treatment of rats with the potent pneumotoxin MCT indu ces temporal alterations in TN synthesis/deposition in the affected lu ngs. MCT produced progressive pathological alterations in the cardiopu lmonary system, including increased dry lung weight, right ventricular hypertrophy, and pulmonary hypertension by days 7, 14, and 21, respec tively. TN positive foci were first observed in the parenchyma surroun ding small muscularized pulmonary arteries in MCT-treated rats at day 4; these foci became both more pronounced and frequent as the disease progressed. TN was also observed in the media of the intrapulmonary ar tery at day 21. Northern analysis demonstrated increases in TN transcr ipts in MCT-treated rats as early as day 1. Furthermore, a unique tran script, apparently lacking some fibronectin type III-like units, was o bserved in mRNA extracted from these rats. These data demonstrate alte rations in TN synthetic capacity and focal increases in TN deposition in lungs from MCT-treated rats and suggest that TN may be associated w ith the pathogenesis of pulmonary hypertension.