Generalised reduction of putative endothelial progenitors and CXCR4-positive peripheral blood cells in type 2 diabetes

Diabetologia. 2008 Jul;51(7):1296-305. doi: 10.1007/s00125-008-0939-6. Epub 2008 Feb 20.

Abstract

Aims/hypothesis: In patients with type 2 diabetes, reduced levels of circulating endothelial progenitor cells have been reported and these have been correlated with disease severity. In this study, we examined a panel of markers widely used to identify progenitor and/or stem cells, and determined their association with disease severity in diabetic patients. Since expression of chemokine (C-X-C motif) receptor 4 (CXCR4) has been associated with mobilisation and recruitment of progenitor cells, CXCR4 expression was also analysed.

Methods: Peripheral blood mononuclear cells (PBMCs) from 98 patients with type 2 diabetes and 39 control individuals were analysed by flow cytometry for surface marker expression.

Results: Cells expressing different combinations of progenitor and/or stem cell markers were severely reduced in PBMCs of diabetic patients compared with those of control participants. Moreover, a number of these putative progenitor cell populations were negatively associated with disease severity. Reduced expression of CXCR4 and CD34/CXCR4-positive cells was also observed in diabetic patients. PBMCs expressing CXCR4 positively correlated with levels of progenitor cells in control participants but not in diabetic patients. Levels of putative progenitor and CXCR4-positive cells were further decreased in patients with diabetic complications, including cardiovascular and microvascular diseases.

Conclusions/interpretation: A generalised decrease in a range of progenitor cell populations was observed in type 2 diabetic patients. This reduction was also negatively associated with disease severity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Antigens, CD / metabolism
  • Antigens, CD34 / metabolism
  • Biomarkers / metabolism
  • Diabetes Mellitus, Type 2 / immunology*
  • Diabetes Mellitus, Type 2 / pathology*
  • Diabetic Angiopathies / immunology
  • Diabetic Angiopathies / pathology
  • Endothelial Cells / cytology*
  • Female
  • Flow Cytometry
  • Glycoproteins / metabolism
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Male
  • Middle Aged
  • Peptides / metabolism
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Proto-Oncogene Proteins c-kit / metabolism
  • Receptors, CXCR4 / immunology
  • Receptors, CXCR4 / metabolism*
  • Severity of Illness Index
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antigens, CD34
  • Biomarkers
  • CXCR4 protein, human
  • Glycoproteins
  • Peptides
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, CXCR4
  • Proto-Oncogene Proteins c-kit
  • Vascular Endothelial Growth Factor Receptor-2