title: Exogenous application of transforming growth factor beta 1 stimulates arteriogenesis in the peripheral circulation.
abstract: 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.
authors.affiliation: Max Planck Institute for Physiological and Clinical Research, Department of Experimental Cardiology, Bad Nauheim, Germany. n.vanroyen@amc.uva.nl
authors.forename: Niels
authors.initials: N
authors.lastname: van Royen
authors.forename: Imo
authors.initials: I
authors.lastname: Hoefer
authors.forename: Ivo
authors.initials: I
authors.lastname: Buschmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Heil
authors.forename: Sawa
authors.initials: S
authors.lastname: Kostin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Deindl
authors.forename: Sabina
authors.initials: S
authors.lastname: Vogel
authors.forename: Thomas
authors.initials: T
authors.lastname: Korff
authors.forename: Helmut
authors.initials: H
authors.lastname: Augustin
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schaper
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003097:Collateral Circulation / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors; D006801:Humans; D008222:Lymphokines / Q000037:antagonists & inhibitors; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D016177:Macrophage-1 Antigen; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors