alpha-smooth-muscle actin and microvascular precursor smooth-muscle cells in pulmonary hypertension

Little is known of the molecular basis of smooth-muscle cell development in the microvessels of the adult lung in pulmonary hypertension (PH). Using q uantitative and immunogold electron microscopy techniques we report the dev elopment of microvascular precursor smooth-muscle cells (PSMCs) expressing alpha-smooth-muscle actin (alpha SMA), a first marker of smooth-muscle cell differentiation, in rats with hyperoxic PH. Increase in the frequency of d istal (alveolar wall) vessels with alpha SMA cells preceded (P-chi 2 < 0.02 , Day 4) the increase in proximal (alveolar duct) vessels (P-chi 2 < < 0.02 , Day 14). The smallest vessel with cells expressing alpha SMA (< 50 mu m i n diameter) increased most with time (P-chi 2 < 0.001). Immunopositive PSMC s were rare in normal lung and frequent in hyperoxia, Well-developed filame nt arrays decorated with alpha SMA were detected in intermediate cells earl y in hyperoxia (Day 4). Similar filament networks were detected later in fi broblasts recruited to vessel walls (Days 7 to 14). By Day 28, cells derive d from fibroblasts formed several layers in the vessel wall and expressed d ense alpha SMA filament arrays, in either a central domain or mesh. Thus, i ntermediate cells are the source of cells expressing alpha SMA early in the microvessels in hyperoxic pulmonary hypertension and fibroblasts of cells in the late stage-the time of intense neomuscularization of the microvessel s.