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


OBJECTIVE
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.
Division of Rheumatology & Immunology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong. temy@hkucc.hku.hk
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Mok
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Yiu
C Y
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Wong
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Qiuwaxi
W H
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Lai
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Wong
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Tse
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Lau
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000000981:diagnostic imaging; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism*; D012039:Regional Blood Flow; D045743:Scleroderma, Diffuse / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D045745:Scleroderma, Limited / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D012720:Severity of Illness Index; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology
D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2