Format

Send to:

Choose Destination
See comment in PubMed Commons below
Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):751-7. Epub 2006 Jan 26.

Granulocyte colony-stimulating factor-mobilized circulating c-Kit+/Flk-1+ progenitor cells regenerate endothelium and inhibit neointimal hyperplasia after vascular injury.

Author information

  • 1Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.

Abstract

BACKGROUND:

Granulocyte colony-stimulating factor (G-CSF) treatment was shown to inhibit neointimal formation of balloon-injured vessels, whereas neither the identification of progenitor cells involved in G-CSF-mediated endothelial regeneration with a bone marrow (BM) transplant experiment nor the functional properties of regenerated endothelium have been studied.

METHODS AND RESULTS:

Recombinant human G-CSF (100 microg/kg per day) was injected daily for 14 days starting 3 days before balloon injury in the rat carotid artery. Neointimal formation of denuded vessels on day 14 was markedly attenuated by G-CSF (39% versus the control; P<0.05). Endothelial cell-specific immunostaining revealed an enhancement of re-endothelialization (1.8-fold increase versus the control; P<0.05) and inhibition of extravasation of Evans Blue dye (47%; P=0.02). The regenerated endothelium exhibited acetylcholine-mediated vasodilatation in NO-dependent manner. G-CSF increased the circulating c-Kit+/Flk-1+ cells (9.1-fold; P<0.02), which showed endothelial properties in vitro (acetylated low-density lipoprotein uptake and lectin binding) and incorporated into the regenerated endothelium in vivo. A BM replacement experiment with green fluorescent protein (GFP)-overexpressing cells showed that BM-derived GFP+/CD31+ endothelial cells occupied 39% of the total luminal length in the G-CSF-mediated neo-endothelium (2% in the control).

CONCLUSIONS:

The G-CSF-induced mobilization of BM-derived c-Kit+/Flk-1+ cells contributes to endothelial regeneration, and this cytokine therapy may be a feasible strategy for the promotion of re-endothelialization after angioplasty.

PMID:
16439710
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire
    Loading ...
    Write to the Help Desk