The most widely used agents to promote angiogenesis are growth factors known as VEGF and FGF. However, in clinical settings, these have only been able to form new and stable blood vessels for a limited time. VEGF may also cause abnormal vascular leaks and aberrant masses of blood vessels. Recently, another factor – a neurotrophic factor called BDNF (brain derived neurotrophic factor) – has been shown to regulate the vasculature of the developing heart, but the mechanism for this interesting action was unclear.
In the March 1 issue of the Journal of Clinical Investigation, Shahin Rafii and Barbara Hempstead along with colleagues from Cornell University, delve into the mechanisms underlying the angiogenic effects of BDNF in adult blood vessels.
The researchers show that BDNF and VEGF have comparable efficacy in inducing growth of tiny blood vessels in organs that contain cells that express the BDNF receptor TrkB. The also show that BDNF is as effective as VEGF in promoting recovery of the blood flow and vessel density in ischemic limbs. BDNF has local effects on TrkB expressing cells and also recruits a subset of blood stem cells that contribute to neo-angiogenesis. This special population of cells responds specifically to BDNF and contributes to neovascularization.
In an accompanying commentary, Dan Duda and Rakesh Jain write, "This work establishes that neurotrophins are novel proangiogenic factors. Understanding the molecular and cellular underpinnings of this interaction may prove to be crucial for both regenerative medicine and cancer therapy."
Therapy with BDNF may increase the number of functional and stable blood vessels in patients with insufficient blood supply to various organs -– diseases of vascular insufficiency. The selective angiogenic activity of BDNF compared to other growth factors, could lead to the development of organ specific angiogenesis therapy. BDNF now is a novel therapeutic protein to induce organ specific angiogenesis to increase the number of functional and stable vessels.
TITLE: Neurotrophins promote revascularization by local recruitment of TrkB+ endothelial cells and systemic mobilization of hematopoietic progenitors
AUTHOR CONTACT:
Shahin Rafii
Cornell Medical School, New York, NY USA
Phone: (212) 746-2070; Fax: (212) 746-8866; E-mail: srafii@med.cornell.edu
This article is available at: http://www.jci.org/cgi/content/full/115/3/653
ACCOMPANYING COMMENTARY:
TITLE: Pleiotropy of tissue-specific growth factors: from neurons to vessels via bone marrow
AUTHOR CONTACT:
Rakesh K. Jain
Harvard Medical School, Boston, MA USA
Phone: (617) 726-4083; Fax: (617) 724-1819; E-mail: jain@steele.mgh.harvard.edu
This article is available at: http://www.jci.org/cgi/content/full/115/3/596
Journal
Journal of Clinical Investigation