title: Mechanical strain tightly controls fibroblast growth factor-2 release from cultured human vascular smooth muscle cells.
abstract: Although fibroblast growth factor-2 (FGF-2) participates in the response to vascular injury, the role of cellular deformation in FGF-2 release is incompletely understood. To test the hypothesis that mechanical strain tightly controls FGF-2 release, a novel device was used to impose homogeneous and uniform biaxial strain to human vascular smooth muscle cells. Release of FGF-2 increased with the number of cycles of strain (14%, 1 Hz); 1, 9, and 90 cycles of strain, respectively, released 0.55 +/- 0.06%, 2.9 +/- 0.3%, and 5.5 +/- 1.3% of the total cellular FGF-2 (versus 0.00 +/- 0.40% for control, P < .05), but release was not further increased for strain of 90 to 90,000 cycles. Mechanical release of FGF-2 depended on both the frequency and amplitude of deformation. For example, strain (90 cycles, 1 Hz) at 4% amplitude released only 0.1 +/- 0.1% of the total FGF-2, but strain at 14% and 33% amplitudes, respectively, released 5.7 +/- 0.5% and 19.0 +/- 3.0% of the FGF-2 cellular pool (P < .05), suggesting a strain amplitude threshold for FGF-2 release. Injury to a subpopulation of cells increased with the frequency and amplitude of strain, but cells were not injured by strains below 10% amplitude. Strain following pretreatment with heparin released 12.6 +/- 1.6% of the total FGF-2 (versus 15.8 +/- 0.9% for strain alone, P < .05), indicating that most FGF-2 was liberated from the nuclear or cytoplasmic pools and not from low-affinity extracellular receptors. Conversely, strain in the presence of heparin released 25.2 +/- 3.5% of the total FGF-2 (versus 15.6 +/- 2.6% for strain alone, P < .05). Thus, cellular strain closely modulates the release of intracellular FGF-2 from human vascular smooth muscle cells, but FGF-2 release is negligible in response to the smaller strains that occur in the normal artery. In addition, larger mechanical strains lead to transfer of intracellular FGF-2 to the extracellular low-affinity receptors, where FGF-2 may be displaced by heparin. These observations provide insight into the mechanisms by which deforming vascular injury, such as that produced by arterial interventions, may elicit a proliferative response.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston Mass 02115, USA.
authors.forename: G C
authors.initials: GC
authors.lastname: Cheng
authors.forename: W H
authors.initials: WH
authors.lastname: Briggs
authors.forename: D S
authors.initials: DS
authors.lastname: Gerson
authors.forename: P
authors.initials: P
authors.lastname: Libby
authors.forename: A J
authors.initials: AJ
authors.lastname: Grodzinsky
authors.forename: M L
authors.initials: ML
authors.lastname: Gray
authors.forename: R T
authors.initials: RT
authors.lastname: Lee
mesh_terms: D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D011956:Receptors, Cell Surface; D016222:Fibroblast Growth Factor 2