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Early outgrowth EPCs generation is reduced in patients with Buerger’s disease

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Abstract

Background

Buerger’s disease often shows poor collateral artery generation (i.e. neovascularization) in the ischemic limbs. However, the etiology has not yet been clarified. Circulating endothelial progenitor cells (EPCs) derived from bone marrow contribute to neovascularization in the multi-step process which includes the following capacities; mobilization, differentiation, adhesion, migration, invasion and secretion.

Materials and methods

We assessed EPCs capacities in vitro and ex vivo in age- and sex-matched controls (n = 12) and patients with Buerger’s disease (n = 12), derived from peripheral blood-derived mononuclear cells (PB-MNCs).

Results

In the flow cytometry analysis, the numbers of circulating EPC (CD34+/KDR+ or CD133+/KDR+ PB-MNC) were similar between controls and patients with Buerger’s disease. Next, we cultured PB-MNC to obtain EPCs. The number of early outgrowth EPCs was significantly decreased in patients with Buerger’s disease (p < 0.005), indicating the reduced generation of early outgrowth EPCs in Buerger’s disease. However, adhesion, migration, invasion and secretion capacities were not impaired in patients with Buerger’s disease.

Conclusions

The early outgrowth EPCs generation is reduced in patients with Buerger’s disease.

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Abbreviations

EPCs:

Endothelial progenitor cells

PB-MNCs:

Peripheral blood-derived mononuclear cells

TAO:

Thromboangiitis obliterans

ECs:

Endothelial cells

KDR:

Kinase domain receptor

VEGF:

Vascular endothelial growth factor

FACS:

Fluorescence-activated cell sorting

HUVEC:

Human umbilical vein endothelial cell

Dil-acLDL:

1,1′-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine-labeled acetylated low-density lipoprotein

DAPI:

4′,6-diamidino-2-phenylindole

b-FGF:

Basic fibroblast growth factor

PDGF-BB:

Platelet-derived growth factor BB

IGF:

Insulin growth factor

SDF-1α:

Stromal cell-derived factor-1α

ELISA:

Enzyme-linked immunosorbent assay

IL-1, -6, -8:

Interleukin-1, -6, -8

TGF-1α:

Tumor growth factor-1α

VCAM-1:

Vascular cell adhesion molecule-1

MCP-1:

Monocyte chemotactic protein-1

hs-CRP:

High-sensitivity C-reactive protein

m-RNA:

Messenger ribonucleic acid

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Acknowledgments

We thank to Kimiko Kimura in the cardiovascular research institute, Kurume University for her excellent technical supports in the flow cytometric analysis and ELISA. This study was supported by Research Grants from The Ministry of Education, Science and Culture, Research on Human Genome, Tissue Engineering Food Biotechnology, and the Ministry of Health, Labor and Welfare, The Mochida Memorial Foundation for Medical and Pharmaceutical Research, Kaibara Morikazu Medical Science Promotion Foundation and Kimura Memorial Heart Foundation Research, Japan.

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There is no conflict of interest or financial disclosure by the authors.

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Correspondence to Ken-ichiro Sasaki.

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Katsuki, Y., Sasaki, Ki., Toyama, Y. et al. Early outgrowth EPCs generation is reduced in patients with Buerger’s disease. Clin Res Cardiol 100, 21–27 (2011). https://doi.org/10.1007/s00392-010-0198-7

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  • DOI: https://doi.org/10.1007/s00392-010-0198-7

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