Donate Help Contact The AHA Sign In Home
American Heart Association
Arteriosclerosis, Thrombosis, and Vascular Biology
Search: search_blue_button Advanced Search
Published Online
on February 20, 2003

Arteriosclerosis, Thrombosis, and Vascular Biology. 2003
Published online before print February 20, 2003, doi: 10.1161/01.ATV.0000062883.93715.37
A more recent version of this article appeared on April 1, 2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
23/4/594    most recent
01.ATV.0000062883.93715.37v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Donohue, P. J.
Right arrow Articles by Winkles, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Donohue, P. J.
Right arrow Articles by Winkles, J. A.
Related Collections
Right arrow Arrythmias-basic studies
Right arrow Genetics of cardiovascular disease

Submitted on January 22, 2003
Accepted on February 5, 2003

TWEAK Is an Endothelial Cell Growth and Chemotactic Factor That Also Potentiates FGF-2 and VEGF-A Mitogenic Activity

Patrick J. Donohue ; Christine M. Richards ; Sharron A.N. Brown ; Heather N. Hanscom ; John Buschman ; Shobha Thangada ; Timothy Hla ; Mark S. Williams ; and Jeffrey A. Winkles *

From the Departments of Vascular Biology (P.J.D., C.M.R., S.A.N.B., H.N.H., J.B., J.A.W.) and Immunology (M.S.W.), Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, Md; the Departments of Biochemistry and Molecular Biology (J.A.W.) and Immunology (M.S.W.) and the Institute for Biomedical Sciences (J.A.W., M.S.W.), George Washington University Medical Center, Washington, DC; and the Center for Vascular Biology (S.T., T.H.,), Department of Physiology, University of Connecticut Health Center, Farmington, Conn.

* To whom correspondence should be addressed. E-mail: winkles{at}usa.redcross.org.

Objective--TWEAK, a member of the tumor necrosis factor superfamily, binds to the Fn14 receptor and stimulates angiogenesis in vivo. In this study, we investigated Fn14 gene expression in human endothelial cells (ECs) and examined the effect of TWEAK, added either alone or in combination with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor-A (VEGF-A), on EC proliferation, migration, and survival in vitro. We also determined whether a soluble Fn14-Fc fusion protein could inhibit TWEAK biologic activity on ECs and investigated TWEAK signal transduction in ECs.

Methods and Results--We found that both FGF-2 and VEGF-A could induce Fn14 mRNA expression in ECs. TWEAK was a mitogen for ECs, and this proliferative activity could be inhibited by an Fn14-Fc decoy receptor. Furthermore, TWEAK treatment activated several intracellular signaling pathways in ECs and potentiated FGF-2- and VEGF-A-stimulated EC proliferation. TWEAK also had EC chemotactic activity, but it did not promote EC survival.

Conclusions--These results indicate that TWEAK is an EC growth and migration factor but not a survival factor. TWEAK can also enhance both FGF-2 and VEGF-A mitogenic activity on ECs. Thus, TWEAK may act alone as well as in combination with FGF-2 or VEGF-A to regulate pathological angiogenesis.
Key words: TWEAK • Fn14, fibroblast growth factor • vascular endothelial growth factor • endothelial cells




This article has been cited by other articles:


Home page
 CJASNHome page
M. I. Yilmaz, J. J. Carrero, A. Ortiz, J. L. Martin-Ventura, A. Sonmez, M. Saglam, H. Yaman, M. Yenicesu, J. Egido, and L. M. Blanco-Colio
Soluble TWEAK Plasma Levels as a Novel Biomarker of Endothelial Function in Patients with Chronic Kidney Disease
Clin. J. Am. Soc. Nephrol., November 1, 2009; 4(11): 1716 - 1723.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. L. Tran, W. S. McDonough, B. A. Savitch, S. P. Fortin, J. A. Winkles, M. Symons, M. Nakada, H. E. Cunliffe, G. Hostetter, D. B. Hoelzinger, et al.
Increased Fibroblast Growth Factor-Inducible 14 Expression Levels Promote Glioma Cell Invasion via Rac1 and Nuclear Factor-{kappa}B and Correlate with Poor Patient Outcome
Cancer Res., October 1, 2006; 66(19): 9535 - 9542.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. De, J.-I. Park, K. Kawamura, R. Chen, C. Klein, R. Rauch, S. M. Mulders, M. D. Sollewijn Gelpke, and A. J. W. Hsueh
Intraovarian Tumor Necrosis Factor-Related Weak Inducer of Apoptosis/Fibroblast Growth Factor-Inducible-14 Ligand-Receptor System Limits Ovarian Preovulatory Follicles from Excessive Luteinization
Mol. Endocrinol., October 1, 2006; 20(10): 2528 - 2538.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
B. Munoz-Garcia, J. L. Martin-Ventura, E. Martinez, S. Sanchez, G. Hernandez, L. Ortega, A. Ortiz, J. Egido, and L. M. Blanco-Colio
Fn14 Is Upregulated in Cytokine-Stimulated Vascular Smooth Muscle Cells and Is Expressed in Human Carotid Atherosclerotic Plaques: Modulation by Atorvastatin
Stroke, August 1, 2006; 37(8): 2044 - 2053.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Campbell, L. C. Burkly, H.-X. Gao, J. W. Berman, L. Su, B. Browning, T. Zheng, L. Schiffer, J. S. Michaelson, and C. Putterman
Proinflammatory Effects of Tweak/Fn14 Interactions in Glomerular Mesangial Cells
J. Immunol., February 1, 2006; 176(3): 1889 - 1898.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
R. Polavarapu, M. C. Gongora, J. A. Winkles, and M. Yepes
Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Increases the Permeability of the Neurovascular Unit through Nuclear Factor-{kappa}B Pathway Activation
J. Neurosci., November 2, 2005; 25(44): 10094 - 10100.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Felli, F. Pedini, A. Zeuner, E. Petrucci, U. Testa, C. Conticello, M. Biffoni, A. Di Cataldo, J. A. Winkles, C. Peschle, et al.
Multiple Members of the TNF Superfamily Contribute to IFN-{gamma}-Mediated Inhibition of Erythropoiesis
J. Immunol., August 1, 2005; 175(3): 1464 - 1472.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. L. Tran, W. S. McDonough, B. A. Savitch, T. F. Sawyer, J. A. Winkles, and M. E. Berens
The Tumor Necrosis Factor-like Weak Inducer of Apoptosis (TWEAK)-Fibroblast Growth Factor-inducible 14 (Fn14) Signaling System Regulates Glioma Cell Survival via NF{kappa}B Pathway Activation and BCL-XL/BCL-W Expression
J. Biol. Chem., February 4, 2005; 280(5): 3483 - 3492.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Yepes, S. A.N. Brown, E. G. Moore, E. P. Smith, D. A. Lawrence, and J. A. Winkles
A Soluble Fn14-Fc Decoy Receptor Reduces Infarct Volume in a Murine Model of Cerebral Ischemia
Am. J. Pathol., February 1, 2005; 166(2): 511 - 520.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. H. Ho, H. Vu, S. A. N. Brown, P. J. Donohue, H. N. Hanscom, and J. A. Winkles
Soluble Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Overexpression in HEK293 Cells Promotes Tumor Growth and Angiogenesis in Athymic Nude Mice
Cancer Res., December 15, 2004; 64(24): 8968 - 8972.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
K. Tanabe, I. Bonilla, J. A. Winkles, and S. M. Strittmatter
Fibroblast Growth Factor-Inducible-14 Is Induced in Axotomized Neurons and Promotes Neurite Outgrowth
J. Neurosci., October 22, 2003; 23(29): 9675 - 9686.
[Abstract] [Full Text] [PDF]


ATVB Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2003 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.