Neurotrophins promote revascularization by local recruitment of TrkB+ endothelial cells and systemic mobilization of hematopoietic progenitors. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Animals
  • Biomarkers
  • Cell Line
  • Chemotaxis
  • Female
  • Genetic Vectors
  • Humans
  • Ischemia
  • Male
  • Mice
  • Mice, Inbred Strains
  • Rats
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2

MeSH Major

  • Brain-Derived Neurotrophic Factor
  • Endothelial Cells
  • Hematopoietic Stem Cells
  • Neovascularization, Physiologic
  • Nerve Growth Factors
  • Receptor, trkB

abstract

  • The neurotrophin brain-derived neurotrophic factor (BDNF) is required for the maintenance of cardiac vessel wall stability during embryonic development through direct angiogenic actions on endothelial cells expressing the tropomysin receptor kinase B (TrkB). However, the role of BDNF and a related neurotrophin ligand, neurotrophin-4 (NT-4), in the regulation of revascularization of the adult tissues is unknown. To study the potential angiogenic capacity of BDNF in mediating the neovascularization of ischemic and non-ischemic adult mouse tissues, we utilized a hindlimb ischemia and a subcutaneous Matrigel model. Recruitment of endothelial cells and promotion of channel formation within the Matrigel plug by BDNF and NT-4 was comparable to that induced by VEGF-A. The introduction of BDNF into non-ischemic ears or ischemic limbs induced neoangiogenesis, with a 2-fold increase in the capillary density. Remarkably, treatment with BDNF progressively increased blood flow in the ischemic limb over 21 days, similar to treatment with VEGF-A. The mechanism by which BDNF enhances capillary formation is mediated in part through local activation of the TrkB receptor and also by recruitment of Sca-1+CD11b+ pro-angiogenic hematopoietic cells. BDNF induces a potent direct chemokinetic action on subsets of marrow-derived Sca-1+ hematopoietic cells co-expressing TrkB. These studies suggest that local regional delivery of BDNF may provide a novel mechanism for inducing neoangiogenesis through both direct actions on local TrkB-expressing endothelial cells in skeletal muscle and recruitment of specific subsets of TrkB+ bone marrow-derived hematopoietic cells to provide peri-endothelial support for the newly formed vessels.

publication date

  • March 2005

has subject area

  • Adenoviridae
  • Animals
  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Cell Line
  • Chemotaxis
  • Endothelial Cells
  • Female
  • Genetic Vectors
  • Hematopoietic Stem Cells
  • Humans
  • Ischemia
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neovascularization, Physiologic
  • Nerve Growth Factors
  • Rats
  • Receptor, trkB
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1051987

Digital Object Identifier (DOI)

  • 10.1172/JCI22655

PubMed ID

  • 15765148

Additional Document Info

start page

  • 653

end page

  • 663

volume

  • 115

number

  • 3