The effect of brain-derived neurotrophic factor on angiogenesis

Abstract

To investigate the in vitro and in vivo proangiogenic effects of brain-derived neurotrophic factor (BDNF), human umbilical vein endothelial cells (HUVECs) were isolated and cultured in primary culture. The effect of BDNF on the proliferation of HUVECs was examined by MTT assay. The effects of BDNF on HUVEC migration and tube formation were studied by modified Boyden chamber assay and tube formation assay, respectively. Matrigel plug assay and chorioallantoic membrane assay were used to evaluate the effects of BDNF on angiogenesis in vivo. Our results showed that BDNF substantially stimulated the migration and tube formation of HUVECs in vitro, although it did not induce HUVEC proliferation. BDNF also induced angiogenesis both in matrigel plug of mouse model and in chick chorioallantoic membrane. In conclusion, BDNF can promote angiogenesis both in vitro and in vivo, and may be a proangiogenic factor.

Keywords

brain-derived neurotrophic factor / angiogenesis / human umbilical vein endothelial cells

References

[1] LinY.L.. The research advance of brain derived neurotrophic factor. Lett Biotechnol, 2003, 14(3): 241-244

[2] SeiferD.B., FengB., SheldenR.M., et al. . Brain derived neurotrophic factor: a novel human ovarian follicular protein. J Clin Endocrinol Metab, 2002, 87(2): 655-659

[3] LabouyrieE., DubusP., GroppiA., et al. . Expression of neurotrophins and their receptors in human bone marrow. Am J Pathol, 1999, 154(2): 405-415

[4] RicciA., GrecoS., AmentaF., et al. . Neurotrophins and neurotrophin receptors in human pulmonary arteries. J Vasc Res, 2000, 37(5): 355-363

[5] HuY., SunC.Y., WangY.D., et al. . Study on the high expression of brain-derived neurotrophic factor in multiple myeloma patients and its possible mechanism. Zhongguo Shi Yan Xue Ye Xue Za Zhi (Chinese), 2005, 13(1): 104-109

[6] KallmannB.A., WagnerS., HummelV., et al. . Characteristic gene expression profile of primary human cerebral endothelial cells. FASEB J, 2002, 16(6): 589-591

[7] NakahashiT., FujimuraH., AltarC.A., et al. . Vascular endothelial cells synthesize and secrete brain-derived neurotrophic factor. FEBS Lett, 2000, 470(2): 113-117

[8] NemotoK., FukamachiK., NemotoF., et al. . Gene expression of neurotrophins and their receptors in cultured rat vascular smooth muscle cells. Biochem Biophys Res Commun, 1998, 245(1): 284-288

[9] JaffeE.A., NachmanR.L., BeckerC.G., et al. . Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest, 1973, 52(11): 2745-2756

[10] RibattiD., GualandrisA., BastakiM., et al. . New model for the study of angiogenesis in the chick embryo chorioallantoic membrane. J Vasc Res, 1997, 34(6): 455-463

[11] BussolinoF., MantovaniA., PersicoG.. Molecular mechanisms of blood vessel formation. Trends Biochem Sci, 1997, 22(7): 251-256

[12] CarmelietP.. Mechanisms of angiogenesis and arteriogenesis. Nat Med, 2000, 6(4): 389-395

[13] MüllerD., DavidoffM.S., BargheerO., et al. . The expression of neurotrophins and their receptors in the prenatal and adult human testis: evidence for functions in Leydig cells. Histochem Cell Biol, 2006, 126(2): 199-211

[14] DonovanM.J., MirandaR.C., KraemerR., et al. . Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regulation of expression in response to injury. Am J Pathol, 1995, 147(2): 309-324

[15] DonovanM.J., LinM.I., WiegnP., et al. . Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization. Development, 2000, 127(21): 4531-4540

[16] KermaniP., RafiiD., JinD.K., et al. . Neurotrophins promote revascularization by local recruitment of TrkB⁺ endothelial cells and systemic mobilization of hematopoietic progenitors. J Clin Invest, 2005, 115(3): 653-663

[17] VaccaA., RibattiD., PrestaM., et al. . Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood, 1999, 93(9): 3064-3073

[18] MunshiN.C., WilsonC.. Increased bone marrow microvessel density in newly diagnosed multiple myeloma carries a poor prognosis. Semi Oncol, 2001, 28(6): 565-569

[19] YangR.C., HanZ.C.. Angiogenesis in hematologic malignancies and its clinical implications. Intern J Hematol, 2002, 75(3): 246-256

[20] BhattiS.S., KumarL., DindaA.K., et al. . Prognostic value of bone marrow angiogenesis in multiple myeloma: use of light microscopy as well as computerized image analyzer in the assessment of microvessel density and total vascular area in multiple myeloma and its correlation with various clinical, histological, and laboratory parameters. Am J Hematol, 2006, 81(9): 649-656

[21] KleinB., ZhangX.G., LuZ.Y., et al. . Interleukin-6 in human multiple myeloma. Blood, 1995, 85(4): 863-872

[22] KumarS., WitzigT.E., TimmM., et al. . Expression of VEGF and its receptors by myeloma cells. Leukemia, 2003, 17(10): 2025-2031

[23] TaiY.T., PodarK., CatleyL., et al. . Insulin-like growth factor-1 induces adhesion and migration in human multiple myeloma cells via activation of beta1-integrin and phosphatidylinositol 3′-kinase/AKT signaling. Cancer Res, 2003, 63(18): 5850-5858

[24] DerksenP.W., de GorterD.J., MeijerH.P., et al. . The hepatocyte growth factor/Met pathway controls proliferation and apoptosis in multiple myeloma. Leukemia, 2003, 17(4): 764-774

[25] SmolejL., AndrýsC., MaisnarV., et al. . Plasma concentrations of vascular endothelial growth factor and basic fibroblast growth factor in lymphoproliferative disorders. Acta Medica (Hradec Kralove), 2005, 48(1): 57-58

[26] KowalskiP.J., PaulinoA.F.. Perineural invasion in adenoid cystic carcinoma: Its causation/promotion by brain-derived neurotrophic factor. Hum Pathol, 2002, 33(9): 933-936

[27] SatohF., MimataH., NomuraT., et al. . Autocrine expression of neurotrophins and their receptors in prostate cancer. Int J Urol, 2001, 8(7): S28-S34

[28] FengX., JiangH., BaikJ.C., et al. . BDNF dependence in neuroblastoma. J Neurosci Res, 2001, 64(4): 355-363

[29] HuY., SunC.Y., WangH.F., et al. . Brain-derived neurotrophic factor promotes growth and migration of multiple myeloma (MM) cells. Cancer Genet Cytogenet, 2006, 169(1): 12-20

[30] SakamotoY., KitajimaY., EdakuniG., et al. . Expression of Trk tyrosine kinase receptor is a biologic marker for cell proliferation and perineural invasion of human pancreatic ductal adenocarcinoma. Oncol Rep, 2001, 8(3): 477-484

[31] JaboinJ., KimC.J., KaplanD.R., et al. . Brain-derived neurotrophic factor activation of TrκB protects neuroblastoma cells from chemotherapy-induced apoptosis via phosphatidylinositol 3′-kinase pathway. Cancer Res, 2002, 62(22): 6756-6763

[32] JaboinJ., HongA., KimC.J., et al. . Cisplatin-induced cytotoxicity is blocked by brain-derived neurotrophic factor activation of TrkB signal transduction path in neuroblastoma. Cancer Lett, 2003, 193(1): 109-114