Document Detail


The profibrotic cytokine transforming growth factor-β1 increases endothelial progenitor cell angiogenic properties.
MedLine Citation:
PMID:  22284809     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Transforming growth factor-β1 (TGF-β1) 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-β1 modulation of EPC angiogenic properties.
METHODS: TGF-β1 plasma levels were determined in 64 patients with IPF and compared with those in controls. The effect of TGF-β1 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-β1 in ECFCs by using short interfering RNA.
RESULTS: Total TGF-β1 plasma levels were significantly increased in patients with IPF as compared with controls (P < 0.0001). TGF-β1 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-β1 receptors.
CONCLUSIONS: TGF-β1 is proangiogenic in vivo and induces ECFC angiogenic properties in vitro, suggesting that TGF-β1 may play a role during vascular remodeling in fibrotic disease states via EPCs.
Authors:
S M Evrard; C d'Audigier; L Mauge; D Israël-Biet; C L Guerin; I Bieche; J C Kovacic; A-M Fischer; P Gaussem; D M Smadja
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  10     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-02     Completed Date:  2012-08-31     Revised Date:  2014-03-21    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  England    
Other Details:
Languages:  eng     Pagination:  670-9     Citation Subset:  IM    
Copyright Information:
© 2012 International Society on Thrombosis and Haemostasis.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT01038700
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Animals
Case-Control Studies
Cell Movement
Cell Survival
Cells, Cultured
Endothelial Cells / metabolism*
Female
Fetal Blood / cytology
France
Hemoglobins / metabolism
Humans
Idiopathic Pulmonary Fibrosis / blood,  metabolism*,  physiopathology
Male
Mice
Mice, Inbred C57BL
Middle Aged
Neovascularization, Physiologic*
Prospective Studies
RNA Interference
Receptors, Transforming Growth Factor beta / genetics,  metabolism
Stem Cells / metabolism*
Transfection
Transforming Growth Factor beta1 / blood,  metabolism*
Up-Regulation
Grant Support
ID/Acronym/Agency:
K08 HL111330/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hemoglobins; 0/Receptors, Transforming Growth Factor beta; 0/TGFB1 protein, human; 0/Transforming Growth Factor beta1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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