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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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