Reduced oxygen tension induces pulmonary endothelium to release a pulmonary smooth muscle cell mitogen(s)

Bovine pulmonary endothelial cells grown in vitro were shown to release a factor that was mitogenic for pulmonary smooth muscle cells during exposure to a reduced oxygen tension atmosphere. The addition of hypoxic endothelium-derived medium resulted in a 60% increase in smooth muscle cell number after 24 h of exposure. Addition of medium from pulmonary endothelium exposed to normoxic conditions or medium derived from either hypoxic or normoxic aortic endothelium did not result in significant increases in smooth muscle cell number. Physicochemical characterization of the hypoxic pulmonary endothelial cell-derived factor(s) showed that it was resistant to heat and reducing agent treatment and stable between pH 3 and 10. The mitogenic activity decreased by 71% at pH 2 and by 68% after treatment with trypsin. The activity adhered to DEAE Sephadex. Gel filtration chromatography of the hypoxic-conditioned medium demonstrated 2 major peaks of smooth muscle cell growth factor activity corresponding to molecular weights between 6,000 and 14,000 and 20,000 and 65,000 daltons, respectively. These data suggest that this pulmonary endothelial cell-derived smooth muscle cell peptide mitogen(s) may be involved in the smooth muscle cell proliferative response seen with chronic alveolar hypoxia.