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

Fibroblast growth factor-2 (FGF-2) is a potent mitogen involved in the response to vascular injury. However, mechanisms controlling FGF-2 release are not clearly understood. We studied the effect of shear stress on the release of FGF-2 from human aortic smooth muscle cells (HASMC) using an in vitro parallel plate flow system. FGF-2 levels were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results indicated that after only 15 minutes of shear stress (25 dyn/cm²), 17% of the total FGF-2 was released from HASMC. FGF-2 levels in circulating medium increased 10-fold versus static controls. A 50% increase in FGF-2 was detected in heparin extracts following shear stress. Furthermore, a significant decrease in FGF-2 was detected in the cell lysate, indicating that FGF-2 was released from inside the cell. Permeability studies using a fluorescent dye were performed to identify transient membrane disruption as the mechanism of FGF-2 release. After cells were sheared in the presence of medium containing FITC-dextran, flow cytometry detected a 50% increase in mean fluorescence versus control cells. This result suggests that flow-induced FGF-2 release is due to transient membrane disruption