The profibrotic cytokine transforming growth factor-ß1 increases endothelial progenitor cell angiogenic properties

被引：39
作者：
Evrard, S. M. [2 ]
D'audigier, C. [2 ]
Mauge, L. [2 ]
Israel-Biet, D. [2 ,3 ]
Guerin, C. L. [2 ,4 ]
Bieche, I. [2 ,5 ,6 ]
Kovacic, J. C. [7 ]
Fischer, A. -M. [2 ]
Gaussem, P. [2 ]
Smadja, D. M. [1 ,2 ,8 ,9 ]
机构：
[1] Hop Europeen Georges Pompidou, AP HP, Dept Hematol, Serv Hematol Biol, Paris, France
[2] Univ Paris 05, Paris, France
[3] Hop Europeen Georges Pompidou, AP HP, Serv Pneumol, Paris, France
[4] Paris Cardiovasc Res Ctr PARCC, INSERM, UMRS 970, Paris, France
[5] INSERM, UMRS 745, Paris, France
[6] Ctr Rene Huguenin, Lab Oncogenet, St Cloud, France
[7] Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA
[8] Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program, Boston, MA USA
[9] Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA USA
来源：
JOURNAL OF THROMBOSIS AND HAEMOSTASIS | 2012年 / 10卷 / 04期
关键词：
endothelial colony-forming cells; endothelial progenitor cells; idiopathic pulmonary fibrosis; TGF-ss; 1; IDIOPATHIC PULMONARY-FIBROSIS; SMOOTH-MUSCLE-CELLS; TGF-BETA; PAR-1; ACTIVATION; IN-VITRO; EXPRESSION; RECEPTORS; DISEASE; FACTOR-BETA(1); MECHANISMS;
D O I：
10.1111/j.1538-7836.2012.04644.x
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Background: Transforming growth factor-beta 1 (TGF-beta 1) is a profibrotic cytokine that plays a major role in vascular biology, and is known to regulate the phenotype and activity of various vascular cell populations. Because most fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), are associated with vascular remodeling, and as endothelial progenitor cells (EPCs) may be involved in this process, we investigated the impact of TGF-beta 1 modulation of EPC angiogenic properties. Methods: TGF-beta 1 plasma levels were determined in 64 patients with IPF and compared with those in controls. The effect of TGF-beta 1 on angiogenesis was studied in vivo in a Matrigel plug model and in vitro on endothelial colony-forming cells (ECFCs). We studied the effects of inhibiting the expression of the three main receptors of TGF-beta 1 in ECFCs by using short interfering RNA. Results: Total TGF-beta 1 plasma levels were significantly increased in patients with IPF as compared with controls (P < 0.0001). TGF-beta 1 had proangiogenic effects in vivo by increasing hemoglobin content and blood vessel formation in Matrigel plugs implanted in C57/Bl6 mice, and in vitro by enhancing ECFC viability and migration. The effects were abolished by silencing the three main TGF-beta 1 receptors. Conclusions: TGF-beta 1 is proangiogenic in vivo and induces ECFC angiogenic properties in vitro, suggesting that TGF-beta 1 may play a role during vascular remodeling in fibrotic disease states via EPCs.
引用
收藏
页码：670 / 679
页数：10
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