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YIA 6 Effects of limb ischaemia-reperfusion and radial artery injury on endothelial function and circulating CD133+/CD34+/VEGFR2+ endothelial progenitor cells
  1. L M Tilling,
  2. J M Hunt,
  3. A Donald,
  4. B Clapp,
  5. P J Chowienczyk
  1. Cardiovascular Division, King's College School of Medicine, London, UK

Abstract

Rationale Circulating endothelial progenitor cells (EPC) increase after cardiovascular (CV) events. Whether this results from ischaemia or endothelial injury is unknown. We investigated effects of limb ischaemia-reperfusion (IR) and endothelial injury (EI) on endothelial function and EPC.

Methodology Healthy subjects (n=42, 18–35 yr) underwent either limb IR generated by cuff inflation, or EI, induced by wire rotation through a cannula. Endothelial function was assessed by flow mediated dilation (FMD) and circulating CD34+/CD133+/VEGFR2+ EPC were enumerated by flow cytometry at baseline, 10 min, 1 h, 6 h, 2 days and 7 days. FMD and cytometry were also performed in patients (n=23, 40–75 yr) after EI from radial sheath insertion for coronary angiography, at baseline, 2 days, 7 days, 1 month and 4 months.

Results Endothelial dysfunction occurred immediately after IR (50% reduction from baseline at 10 min, p<0.001), recovering to baseline after 6 h. After EI FMD fell by 80% (p<0.001), recovering by 2 days. In patients, a sustained fall in FMD after EI remained significant at 1 month. After IR CD133+/CD34+ cells increased after 7 days compared to 1 h (82.1±13/100 000 vs 62.2±8.8/100 000 cells, p<0.05). After EI CD133+/CD34+ cells increased after 7 days compared to baseline (105.3±15.8/100 000 vs 77.9±10.3/100 000 cells, p<0.05). In patients CD133+/VEGFR2+ cells fell at 2 days (by 27.6±11.8/100 000 cells, p<0.05) compared with baseline. There was no significant change in CD133+/CD34+ cells.

Conclusions IR and EI cause significant endothelial dysfunction, proportional to the insult. More severe EI reduces CD133+/VEGFR2+ cells, consistent with consumption during repair. In health, CD133+/CD34+ cells expand after arterial insult. No expansion occurs in patients with CV risk factors, possibly reflecting impaired EPC mobilisation.

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