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Sunday 01 May 2005

Transforming growth factor-beta is activated by plasmin and inhibits smooth muscle cell death in human saphenous vein.

By: George SJ, Johnson JL, Smith MA, Angelini GD, Jackson CL.

J Vasc Res 2005 May-Jun;42(3):247-54

BACKGROUND: The effect of activation of endogenous transforming growth factor-beta (TGF-beta) on smooth muscle cell apoptosis was assessed in human saphenous vein. METHODS: Segments of human saphenous vein, obtained at the time of bypass graft surgery, were cultured for 14 days. During this time, smooth muscle cells accumulated in the intima as a result of proliferation and migration, partly counterbalanced by apoptotic cell death. RESULTS: Addition of exogenous TGF-beta(1) had no effect on smooth muscle cell proliferation or apoptosis. However, antibody neutralization of endogenous TGF-beta(1) caused significant increases in smooth muscle cell death in the media and intima without any change in proliferation. A plasmin inhibitor (alpha-N-acetyl-L-lysine methyl ester), a specific urokinase-type plasminogen activator (uPA) inhibitor (amiloride) and an anti-catalytic anti-uPA antibody all caused decreases in the tissue content of active TGF-beta and increases in smooth muscle cell death in the media and intima. CONCLUSIONS: These data suggest that the amount of TGF-beta in human saphenous vein is sufficient, when in the active form, to protect smooth muscle cells against apoptosis. Adding exogenous TGF-beta(1) has no beneficial effect, but decreasing the amount of active TGF-beta causes smooth muscle cells to undergo apoptosis. Plasmin, generated by uPA, appears to be an important activator of endogenous latent TGF-beta. Copyright (c) 2005 S. Karger AG, Basel.

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