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Vascular endothelial growth factor-B promotes in vivo angiogenesis.
Circ Res. 2003 Jul 25; 93(2):114-23.CircR

Abstract

Vascular endothelial growth factors (VEGFs) and their receptors have emerged as central regulators of the angiogenic process. However, involvement of VEGF-B, one of these factors, in angiogenesis remains obscure. Mice received subcutaneous injection of Matrigel alone or Matrigel with human recombinant protein rhVEGF-B167 or with rhVEGF-A165. After 14 days, cell ingrowth in the Matrigel plug was increased by 2.0- and 2.5-fold in rhVEGF-B167-treated and rhVEGF-A165-treated mice, respectively (P<0.01), in association with a raise in phospho-Akt/Akt (1.8-fold, P<0.01) and endothelial NO synthase (eNOS) (1.80- and 1.60-fold, respectively; P<0.05) protein levels measured by Western blot. VEGF-B-induced cell ingrowth was impaired by treatment with NOS inhibitor (NG-nitro-l-arginine methyl ester; L-NAME, 10 mg/kg per day). Treatment with neutralizing antibody directed against the VEGF-B receptor VEGF-R1 (anti-VEGFR1, 10 microg) completely abrogated VEGF-B-related effects. Proangiogenic effect of VEGF-B was confirmed in a mouse model of surgically induced hindlimb ischemia. Plasmids containing human form of VEGF-A (phVEGF-A165) or VEGF-B (phVEGF-B167 or phVEGF-B186) were administered by in vivo electrotransfer. Angiographic score at day 28 showed significant improvement in ischemic/nonischemic leg ratio by 1.4- and 1.5-fold in mice treated with phVEGF-B167 and phVEGF-B186, respectively (P<0.05). Laser Doppler perfusion data also evidenced a 1.5-fold increase in phVEGF-B167-treated and phVEGF-B186-treated mice (P<0.05). Such an effect was associated with an upregulation of phospho-Akt/Akt and eNOS protein levels in the ischemic legs and was hampered by treatment with anti-VEGFR1. This study demonstrates for the first time that VEGF-B, in part through its receptor VEGF-R1, promotes angiogenesis in association with an activation of Akt and eNOS-related pathways.

Authors+Show Affiliations

INSERM U54, Hôpital Lariboisière, 41 Bd de la Chapelle, 75475 Paris cedex 10, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12805240

Citation

Silvestre, Jean-Sébastien, et al. "Vascular Endothelial Growth factor-B Promotes in Vivo Angiogenesis." Circulation Research, vol. 93, no. 2, 2003, pp. 114-23.
Silvestre JS, Tamarat R, Ebrahimian TG, et al. Vascular endothelial growth factor-B promotes in vivo angiogenesis. Circ Res. 2003;93(2):114-23.
Silvestre, J. S., Tamarat, R., Ebrahimian, T. G., Le-Roux, A., Clergue, M., Emmanuel, F., Duriez, M., Schwartz, B., Branellec, D., & Lévy, B. I. (2003). Vascular endothelial growth factor-B promotes in vivo angiogenesis. Circulation Research, 93(2), 114-23.
Silvestre JS, et al. Vascular Endothelial Growth factor-B Promotes in Vivo Angiogenesis. Circ Res. 2003 Jul 25;93(2):114-23. PubMed PMID: 12805240.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vascular endothelial growth factor-B promotes in vivo angiogenesis. AU - Silvestre,Jean-Sébastien, AU - Tamarat,Radia, AU - Ebrahimian,Teni G, AU - Le-Roux,Aude, AU - Clergue,Michel, AU - Emmanuel,Florence, AU - Duriez,Micheline, AU - Schwartz,Bertrand, AU - Branellec,Didier, AU - Lévy,Bernard I, Y1 - 2003/06/12/ PY - 2003/6/14/pubmed PY - 2003/8/23/medline PY - 2003/6/14/entrez SP - 114 EP - 23 JF - Circulation research JO - Circ Res VL - 93 IS - 2 N2 - Vascular endothelial growth factors (VEGFs) and their receptors have emerged as central regulators of the angiogenic process. However, involvement of VEGF-B, one of these factors, in angiogenesis remains obscure. Mice received subcutaneous injection of Matrigel alone or Matrigel with human recombinant protein rhVEGF-B167 or with rhVEGF-A165. After 14 days, cell ingrowth in the Matrigel plug was increased by 2.0- and 2.5-fold in rhVEGF-B167-treated and rhVEGF-A165-treated mice, respectively (P<0.01), in association with a raise in phospho-Akt/Akt (1.8-fold, P<0.01) and endothelial NO synthase (eNOS) (1.80- and 1.60-fold, respectively; P<0.05) protein levels measured by Western blot. VEGF-B-induced cell ingrowth was impaired by treatment with NOS inhibitor (NG-nitro-l-arginine methyl ester; L-NAME, 10 mg/kg per day). Treatment with neutralizing antibody directed against the VEGF-B receptor VEGF-R1 (anti-VEGFR1, 10 microg) completely abrogated VEGF-B-related effects. Proangiogenic effect of VEGF-B was confirmed in a mouse model of surgically induced hindlimb ischemia. Plasmids containing human form of VEGF-A (phVEGF-A165) or VEGF-B (phVEGF-B167 or phVEGF-B186) were administered by in vivo electrotransfer. Angiographic score at day 28 showed significant improvement in ischemic/nonischemic leg ratio by 1.4- and 1.5-fold in mice treated with phVEGF-B167 and phVEGF-B186, respectively (P<0.05). Laser Doppler perfusion data also evidenced a 1.5-fold increase in phVEGF-B167-treated and phVEGF-B186-treated mice (P<0.05). Such an effect was associated with an upregulation of phospho-Akt/Akt and eNOS protein levels in the ischemic legs and was hampered by treatment with anti-VEGFR1. This study demonstrates for the first time that VEGF-B, in part through its receptor VEGF-R1, promotes angiogenesis in association with an activation of Akt and eNOS-related pathways. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/12805240/Vascular_endothelial_growth_factor_B_promotes_in_vivo_angiogenesis_ L2 - https://www.ahajournals.org/doi/10.1161/01.RES.0000081594.21764.44?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -