© 1997 American Heart Association, Inc.
Articles |
Mechanical Strain Tightly Controls Fibroblast Growth Factor-2 Release From Cultured Human Vascular Smooth Muscle Cells
the Cardiovascular Division, Department of Medicine (G.C.C., W.H.B., D.S.G., P.L., R.T.L.), Brigham and Women's Hospital, Harvard Medical School, Boston Mass, and the Division of Health Sciences and Technology (G.C.C., A.J.G., M.L.G., R.T.L.) and the Department of Mechanical Engineering (A.J.G., R.T.L.), Massachusetts Institute of Technology, Cambridge, Mass.
Correspondence to Richard T. Lee, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. E-mail RTLEE@BICS.BWH.HARVARD.EDU
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.
Key Words: atherosclerosis • biomechanics • vascular smooth muscle • fibroblast growth factor
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