MORPHOLOGICAL AND PROLIFERATIVE RESPONSES OF ENDOTHELIAL-CELLS TO HYDROSTATIC-PRESSURE - ROLE OF FIBROBLAST GROWTH-FACTOR

Subconfluent bovine pulmonary artery endothelial cells on rigid substr ates were exposed to 1.5-15 cm H2O sustained hydrostatic pressure for up to 7 days and exhibited- elongation, cytoskeletal rearrangement, in creased cell proliferation, and bilayering. The role of basic fibrobla st growth factor (bFGF) in the mechanism(s) of these endothelial cell responses to sustained hydrostatic pressure was investigated. Evidence that bFGF was released from endothelial cells exposed to sustained hy drostatic pressure or compression was provided by the following experi mental results: 1) Cells exposed to control (3 mm H2O) pressure displa yed intense nuclear and cytoplasmic bFGF staining by immunocytochemica l techniques; this staining was absent in cells exposed to 10 cm H2O f or 7 days. 2) Conditioned medium from endothelial cells exposed to 10 cm H2O for 7 days contained a transferable, growth-promoting activity exhibiting heparin-Sepharose affinity, lability to both heat and freez e/thawing, and neutralization by anti-bovine bFGF. 3) Suramin (0.1 mM) , a growth-factor receptor inhibitor, abrogated the proliferative and morphological responses of endothelial cells exposed to sustained hydr ostatic pressure. Endothelial cells exposed to elevated hydrostatic pr essure demonstrated no detectable decrement in cell viability as asses sed by Trypan blue exclusion. The results of the present study indicat e that hydrostatic pressure or compression can induce bFGF release fro m endothelial cells independent of cell injury or death; bFGF is subse quently responsible for the morphological, proliferative, and bilayeri ng responses of endothelial cells to hydrostatic pressure. (C) 1993 Wi ley-Liss, Inc.