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Exogenous application of transforming growth factor beta 1 stimulates arteriogenesis in the peripheral circulation

2002; Wiley; Volume: 16; Issue: 3 Linguagem: Inglês

10.1096/fj.01-0563fje

1530-6860

Niels van Royen, Imo E. Hoefer, Ivo Buschmann, Matthias Heil, Sawa Kostin, Elisabeth Deindl, Sabina Vogel, Thomas Korff, Helmut G. Augustin, Christoph Bode, Jan J. Piek, Wolfgang Schäper,

Protease and Inhibitor Mechanisms

Increased expression of transforming growth factor beta1 (TGF-beta1) during collateral artery growth, as well as its numerous effects on monocytes/macrophages and the smooth muscle cell cycle and differentiation, suggest a modulating role for this growth factor during arteriogenesis. We studied the effects of exogenously applied TGF-beta1 on arteriogenesis as well as its interactions with monocytes, endothelial cells, and smooth muscle cells. In a New Zealand White (NZW) rabbit model of femoral artery ligation, increased expression of active TGF-beta1 was found around proliferating arteries in NZW rabbits. The exogenous application of TGF-beta1 led to an increase in both the number of visible collateral arteries as well as the conductance of the collateral circulation (4.0 +/- 0.5 ml/min/100 mmHg vs. 28.9 +/- 3.7 ml/min/100 mmHg, P<0.05). Fluorescence activated cell sorting analysis showed an increase in the expression of the MAC-1 receptor in both rabbit and human monocytes after treatment with TGF-beta1 (control: 91.2 +/- 4.2/482 +/- 21.7; TGF-beta1 200 ng/ml 193.9 +/- 6.7/ 675.5 +/- 25.7, P<0.05 for all differences). TGF-beta1 treated monocytes showed an increased endothelial adhesion and transmigration in transendothelial migration assays (5.75 +/- 0.63 x 10(5) vs. 10.11 +/- 0.04 x 10(5), P<0.05). TGF-beta1 had no direct pro-angiogenic effect on human umbilical vein endothelial cells in a spheroid model of angiogenesis and inhibited the angiogenic effects of vascular endothelial growth factor.