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Exogenous application of transforming growth factor beta 1 stimulates arteriogenesis in the peripheral circulation
Author(s) -
Royen Niels,
Hoefer Imo,
Buschmann Ivo,
Heil Matthias,
Kostin Sawa,
Deindl Elisabeth,
Vogel Sabina,
Korff Thomas,
Augustin Helmut,
Bode Christoph,
Piek Jan J.,
Schaper Wolfgang
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0563fje
Subject(s) - arteriogenesis , transforming growth factor , angiogenesis , umbilical vein , medicine , endocrinology , growth factor , cell sorting , collateral circulation , vascular smooth muscle , chemistry , immunology , receptor , in vitro , flow cytometry , smooth muscle , biochemistry
Increased expression of transforming growth factor β1 (TGF‐ß 1 ) 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‐ß 1 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‐ß1 was found around proliferating arteries in NZW rabbits. The exogenous application of TGF‐ß 1 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‐ß 1 (control: 91.2 ± 4.2/482 ± 21.7; TGF‐ß 1 200 ng/ml 193.9 ± 6.7/ 675.5 ± 25.7, P < 0.05 for all differences). TGF‐ß 1 treated monocytes showed an increased endothelial adhesion and transmigration in transendothelial migration assays (5.75 ± 0.63 × 10 5 vs. 10.11 ± 0.04 × 10 5 , P < 0.05). TGF‐ß 1 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.