Low circulating level of CD133+KDR+cells in patients with systemic sclerosis

Clin Exp Rheumatol. 2010 Sep-Oct;28(5 Suppl 62):S19-25. Epub 2010 Nov 3.

Abstract

Background: Results of previous studies on the level of circulating endothelial progenitor cells (EPCs), which are involved in vascular repair, in scleroderma (SSc) patients have been controversial.

Objectives: To enumerate circulating EPC subsets and to examine their relation with endothelial dysfunction, biochemical markers of endothelial injury and vascular outcome in SSc patients.

Methods: Enumeration of circulating CD34+KDR+ and CD133+ KDR+EPCs was performed by flow cytometry. Endothelium-dependent vasodilation was evaluated by changes in flow-mediated dilation (FMD%) in the brachial artery. Serum level of vascular endothelial growth factor (VEGF) was measured by enzyme linked immunosorbent assay.

Results: SSc patients (n=52) were found to have significantly lower CD133+KDR+EPCs (3.0 vs. 7.0/μl, p<0.001) as well as FMD% (4.8% vs. 7.8%, p<0.001) compared with age and sex-matched controls (n=52). Among patients who had no concomitant cardiovascular risk factors (n=28), CD133+KDR+ EPC level was significantly lower than controls (3.8 vs. 7.3/μl, p=0.001) and correlated modestly with FMD% (r=0.29, p=0.03). Disease duration was the only determining factor identified for circulating CD133+KDR+ EPCs (p=0.03) by logistic regression analysis. Levels of serum VEGF (p=0.92) and KDR expression were not different between patients who had early and intermediate/late disease. Circulating CD34+KDR+ EPCs was not different between SSc patients and controls and did not correlate with any clinical or biochemical parameter.

Conclusions: Lower circulating CD133 +KDR+ EPC subset was found in SSc patients and correlated with impaired endothelium-dependent vasodilation in patients without cardiovascular risk factors suggesting a potential role of deficient EPC recruitment contributing to endothelial dysfunction in this disease.

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism*
  • Biomarkers / metabolism
  • Blood Flow Velocity
  • Brachial Artery / diagnostic imaging
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Female
  • Flow Cytometry
  • Glycoproteins / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Peptides / metabolism*
  • Regional Blood Flow
  • Scleroderma, Diffuse / metabolism
  • Scleroderma, Diffuse / pathology*
  • Scleroderma, Diffuse / physiopathology
  • Scleroderma, Limited / metabolism
  • Scleroderma, Limited / pathology*
  • Scleroderma, Limited / physiopathology
  • Severity of Illness Index
  • Stem Cells / metabolism
  • Stem Cells / pathology*
  • Ultrasonography
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*
  • Vasodilation / physiology

Substances

  • AC133 Antigen
  • Antigens, CD
  • Biomarkers
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2