VASCULAR ENDOTHELIAL GROWTH-FACTOR IS EXPRESSED IN-OVINE PULMONARY VASCULAR SMOOTH-MUSCLE CELLS IN-VITRO AND REGULATED BY HYPOXIA AND DEXAMETHASONE

Chronic lung disease in neonates results from both lung injury and ina dequate repair processes. Little is known about the growth factors inv olved in lung injury and repair, but vascular endothelial growth facto r (VEGF) has recently been reported in several animal models of lung i njury. VEGF is an endothelial cell-specific mitogen, which is also kno wn as vascular permeability factor because of its ability to induce va scular leak in some tissues. Chronic lung disease is complicated by in creased vascular permeability, which can be improved by avoidance of h ypoxia and in some cases by dexamethasone therapy. In many cells, hypo xia stimulates VEGF expression. Also, in some cases, dexamethasone blo cks VEGF expression. This study examined the role of hypoxia and dexam ethasone in regulating the expression of VEGF in pulmonary artery smoo th muscle cells. An ovine VEGF cDNA fragment (453 bp) was cloned and f ound to be highly homologous to known human sequences for VEGF(165). S heep pulmonary artery smooth muscle cells were cultured and exposed to room air, hypoxia, and dexamethasone, alone or in combination for 6 h . At baseline these cells expressed VEGF mRNA at approximately 3.9 kb. The half-life of VEGF mRNA in the smooth muscle cells was 171 min, mo re than 3-fold longer than previous reports for epithelial cells. Expo sure to hypoxia caused a 3-fold increase in mRNA abundance, primarily through transcriptional up-regulation, Dexamethasone blocked the hypox ia-induced increase in VEGF mRNA. The results demonstrate that hypoxia and dexamethasone are regulators of VEGF expression in ovine pulmonar y artery smooth muscle cells. It is not known whether VEGF derived fro m these cells is involved in lung injury and/or normal homeostasis.