Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium .

[en] OBJECTIVE: The endogenous role of the VEGF family member vascular endothelial growth factor-B (VEGF-B) in pathological angiogenesis remains unclear. METHODS AND RESULTS: We studied the role of VEGF-B in various models of pathological angiogenesis using mice lacking VEGF-B (VEGF-B(-/-)) or overexpressing VEGF-B(167). After occlusion of the left coronary artery, VEGF-B deficiency impaired vessel growth in the ischemic myocardium whereas, in wild-type mice, VEGF-B(167) overexpression enhanced revascularization of the infarct and ischemic border zone. By contrast, VEGF-B deficiency did not affect vessel growth in the wounded skin, hypoxic lung, ischemic retina, or ischemic limb. Moreover, VEGF-B(167) overexpression failed to enhance vascular growth in the skin or ischemic limb. CONCLUSIONS: VEGF-B appears to have a relatively restricted angiogenic activity in the ischemic heart. These insights might offer novel therapeutic opportunities

Disciplines :

Anatomy (cytology, histology, embryology...) & physiology

Author, co-author :

Li, X.

Tjwa, M.

Van Hove, I.

Enholm, B.

Neven, E.

Paavonen, K.

Jeltsch, M.

Diez Juan, T.

Sievers, R. E.

Chorianopoulos, E.

More authors (12 more)

Language :

English

Title :

Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium .

Publication date :

September 2008

Journal title :

Arteriosclerosis and Thrombosis: A Journal of Vascular Biology

ISSN :

1049-8834

Publisher :

Scientific Publishing Office American Heart Association, Dallas, United States - Texas

Volume :

Issue :

Pages :

1614-20

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 11 February 2010

Statistics

Number of views

87 (2 by ULiège)

Number of downloads

534 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

109

Bibliography

Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature. 2005; 438:967-974.
Grimmond S, Lagercrantz J, Drinkwater C, Silins G, Townson S, Pollock P, Gotley D, Carson E, Rakar S, Nordenskjold M, Ward L, Hayward NK, Weber G. Cloning and characterization, of a novel human gene related to vascular endothelial growth factor. Genome Research. 1996;6:124-131.
Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson R, Alitalo K, Eriksson U. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci USA. 1996;93:2576-2581.
Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005; 438:932-936.
Tjwa M, Luttun A, Autiero M, Carmeliet P. VEGF and PlGF: two pleiotropic growth factors with distinct roles in development and homeostasis. Cell Tissue Res. 2003;314:5-14.
Nash AD, Baca M, Wright C, Scotney PD. The biology of vascular endothelial growth factor-B (VEGF-B). Pulm. Pharmacol Ther. 2006;19: 61-69.
Li X, Aase K, Li H, von Euler G, Eriksson U. Isoform-specific expression of VEGF-B in normal tissues and tumors. Growth Factors. 2001;19: 49-59.
Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, Gunji Y, Jeltsch MM, Shibuya M, Alitalo K, Eriksson. U. Vascular endothelial growth, factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc Natl Acad Sci. USA. 1998;95:11709-11714.
Aase K, von Euler G, Li X, Ponten A, Thoren P, Cao R, Cao Y, Olofsson B, Gebre-Medhin S, Pekny M, Alitalo K, Betsholtz C, Eriksson U. Vascular endothelial growth factor-B-deficient mice display an atrial conduction, defect. Circulation. 2001;104:358-364.
Bellomo D, Headrick JP, Silins GU, Paterson. CA, Thomas PS, Gartside M, Mould A, Cahill MM, Tonks ID, Grimmond SM, Townson S, Wells C, Little M, Cummings MC, Hayward NK, Kay GF. Mice lacking the vascular endothelial growth factor-B gene (Vegfb) have smaller hearts, dysfunctional coronary vasculature, and impaired recovery from cardiac ischemia. Circ. Res. 2000;86:E29-E35.
Reichelt M, Shi S, Hayes M, Kay G, Batch J, Gole GA, Browning J. Vascular endothelial growth factor-B and retinal vascular development in the mouse. Clin Experiment Ophthalmol. 2003;31:61-65.
Wanstall JC, Gambino A, Jeffery TK, Cahill MM, Bellomo D, Hayward NK, Kay GF. Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension Cardiovase Res. 2002;55:361-368.
Louzier V, Raffestin B, Leroux A, Branellec D, Caillaud JM, Levame M, Eddahibi S, Adnot S. Role of VEGF-B in the lung during development of chronic hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2003;284:L926-L937.
Mould AW, Greco SA, Cahill MM, Tonks ID, Bellomo D, Patterson C, Zoumazi A, Nash A, Scotney P, Hayward NK, Kay GF. Transgenic overexpression of vascular endothelial growth factor-B isoforms by endothelial cells potentiates postnatal vessel growth in vivo and in vitro. Circ Res. 2005;97:e60-e70.
Wright CE. Effects of vascular endothelial growth factor (VEGF)A and VEGFB gene transfer on vascular reserve in a conscious rabbit hindlimb ischaemia model. Clin Exp Pharmacol Physiol. 2002;29:1035-1039.
Silvestre JS, Tamarat R, Ebrahimian TG, Le-Roux A, Clergue M, Emmanuel F, Duriez M, Schwartz B, Branellec D, Levy BI. Vascular endothelial growth factor-B promotes in vivo angiogenesis. Circ Res. 2003;93:114-123.
Tirziu D, Chorianopoulos E, Moodie KL, Palac RT, Zhuang ZW, Tjwa M, Roncal C, Eriksson U, Fu Q, Elfenbein A, Hall AE, Carmeliet P, Moons L, Simons M. Myocardial hypertrophy in the absence of external stimuli is induced, by angiogenesis in mice. J Clin Invest. 2007;117: 3188-3197.
Bhardwaj S, Roy H, Gruchala M, Viita H, Kholova I, Kokina I, Achen MG, Stacker SA, Hedman M, Alitalo K, Yla-Herttuala S. Angiogenic responses of vascular endothelial growth factors in periadventitial tissue. Hum Gene Ther. 2003;14:1451-1462.
Rissanen TT, Markkanen JE, Gruchala M, Heikura T, Puranen. A, Kettunen MI, Kholova I, Kauppinen RA, Achen MG, Stacker SA, Alitalo K, Yla-Herttuala S. VEGF-D is the strongest angiogenic and lymphangiogenic effector among VEGFs delivered into skeletal muscle via adenoviruses. Circ Res. 2003;92:1098-1106.
Fong GH, Klingensmith. J, Wood CR, Rossant J, Breitman ML. Regulation of flt-1 expression during mouse embryogenesis suggests a role in the establishment of vascular endothelium. Dev Dyn. 1996;207:1-10.
Luttun A, Tjwa M, Moons L, Wu Y, Angelillo-Scherrer A, Liao F, Nagy JA, Hooper A, Priller J, De Klerck B, Compernolle V, Daci E, Bohlen P, Dewerchin M, Herbert JM, Fava R, Matthys P, Carmeliet G, Collen D, Dvorak HF, Hicklin DJ, Carmeliet P. Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Fitl. Nat Med. 2002;8: 831-840.
Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, De Mol M, Wu Y, Bono F, Devy L, Beck H, Scholz D, Acker T, DiPalma T, Dewerchin. M, Noel A, Stalmans I, Barra A, Blacher S, Vandendriessche T, Ponten A, Eriksson U, Plate KH, Foidart JM, Schaper W, Chamock-Jones DS, Hicklin DJ, Herbert JM, Collen D, Persico MG. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 2001;7:575-583.
von Degenfeld G, Banfi A, Springer ML, Wagner RA, Jacobi J, Ozawa CR, Merchant MJ, Cooke JP, Blau HM. Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia. Faseb J. 2006;20:2657-2659.
Rusnati M, Presta M. Fibroblast growth factors/fibroblast growth factor receptors as targets for the development of anti-angiogenesis strategies. Curr Pharm. Des. 2007;13:2025-2044.
Aird WC. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res. 2007;100:158-173.
Smart N, Rossdeutsch A, Riley PR. Thymosin beta4 and angiogenesis: modes of action and therapeutic potential. Angiogenesis. 2007;10: 229-241.
Ikuta T, Ariga H, Matsumoto K. Extracellular matrix tenascin-X in combination, with, vascular endothelial growth, factor B enhances endothelial cell proliferation. Genes Cells. 2000;5:913-927.