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

被引:125
作者
van Royen, N
Hoefer, I
Buschmann, I
Heil, M
Kostin, S
Deindl, E
Vogel, S
Korff, T
Augustin, H
Bode, C
Piek, JJ
Schaper, W
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
[2] Max Planck Inst Physiol & Clin Res, Dept Expt Cardiol, D-6350 Bad Nauheim, Germany
[3] Univ Freiburg, Dept Cardiol & Angiol, Res Grp Expt & Clin Arteriogenesis, Freiburg, Germany
[4] Clin Tumorbiol Angiogenesis Res Ctr, Freiburg, Germany
关键词
collateral circulation; angiogenesis; arteries; remodeling; leukocytes;
D O I
10.1096/fj.01-0563fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Increased expression of transforming growth factor beta1 (TGF-beta(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-beta(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-beta(1) was found around proliferating arteries in NZW rabbits. The exogenous application of TGF-beta(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-beta(1) (control: 91.2 +/- 4.2/482 +/- 21.7; TGF-beta(1) 200 ng/ml 193.9 +/- 6.7/675.5 +/- 25.7, P < 0.05 for all differences). TGF-beta(1) 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-beta(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.
引用
收藏
页码:432 / +
页数:28
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