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.