Abstract 440: Increased Migration and Proliferation of Human Venous Valve Wall Smooth Muscle Cells are Mediated by FGF2
Introduction: Lesions causing coronary and peripheral vein graft failure often occur at valves. To test the hypothesis that intrinsic differences in cells of the valve wall contribute to graft failure we measured cell migration from tissue explants and migration and proliferation of cultured cells from valve and non-valve sections of human saphenous vein (HSV).
Methods: After removal of endothelium, HSVs were dissected into an outer wall with adventitia and some media and an inner wall with intima and some media. Cell migration from explants and migration (microchemotaxis chambers) and proliferation of cultured cells at passage 6 were measured.
Results: Cells migrated faster from valve compared to non-valve tissue of the inner wall (Figure A; P<0.01, N=24 veins), but not the outer wall (not shown). PDGF-BB- or serum-mediated migration of valve inner wall smooth muscle cells (VSMC) was greater than with non-valve SMCs (NVSMC; P<0.05, N=6 pairs, 6.5 ± 1.2 vs. 4.2 ± 0.8 fold of control for PDGF-BB and 4.7 ± 0.6 vs. 3.4 ± 0.4 for serum). VSMC also proliferated faster than NVSMC after stimulation with PDGF-BB plus 2% serum (P<0.01, N=6 pairs, 3.3 ± 0.4 vs. 2.2 ± 0.2 fold of control). Finally, a blocking antibody to FGF2 had no effect on PDGF-mediated migration or proliferation of NVSMC (migration: IgG 2.2 ± 0.3 vs anti-FGF2 2.0 ± 0.4, N=6; proliferation: IgG 2.6 ± 0.1 vs anti-FGF2 2.5 ± 0.2, N=7), but largely blocked the enhanced migration and proliferation of VSMC (migration: Figure B; P<0.01, N=6; proliferation: control IgG 3.4 ± 0.3 vs. Anti-FGF2 Ab 2.7 ± 0.3 fold; P<0.01, N=7).
Conclusion: The increased migration and proliferation of VSMC compared to NVSMC is largely mediated by FGF2.
Author Disclosures: S. Kikuchi: None. L. Chen: None. T.N. Wight: Research Grant; Modest; R41 HL106967. N. Azuma: None. M. Sobel: Research Grant; Modest; Department of Veterans Affairs, Veterans Health Administration Merit Review Agency. T. Sasajima: None. A.W. Clowes: Research Grant; Significant; R01 HL30946. R.D. Kenagy: None.
- © 2015 by American Heart Association, Inc.