Fluid flow releases fibroblast growth factor-2 from human aortic smooth muscle cells

This study tested the hypothesis that fluid shear stress regulates the rele ase of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cel ls. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracel lular proteoglycans. To test the hypothesis that shear stress regulates FGF -2 release, cells were exposed to flow, and FGF-2 amounts were measured fro m the conditioned medium, pericellular fi action (extracted by heparin trea tment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm(2) in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium in creased 10-fold over medium from static controls (P<0.01). A 50% increase i n FGF-2 content versus control (P<0.01) was found in the pericellular fract ion (extracted by heparin treatment). Furthermore, a significant decrease i n FGF-2 was detected in the cell lysate, indicating that FGF-2 was released from inside the cell. Cell permeability studies with fluorescent dextran w ere performed to examine whether transient membrane disruption caused FGF-2 release. Flow cytometry detected a 50% increase in mean fluorescence of ce lls exposed to 25 dyne/cm(2) versus control cells. This indicates that the observed FGF-2 release from human aortic smooth muscle cells is likely due to transient membrane disruption on initiation of flow.