Vascular injury causes acute systemic inflammation and mobilizes endothelial progenitor cells (EPCs) and endothelial cell (EC) colony-forming units (EC-CFUs). Whether such mobilization occurs as part of a nonspecific acute phase response or is a phenomenon specific to vascular injury remains unclear. We aimed to determine the effect of acute systemic inflammation on EPCs and EC-CFU mobilization in the absence of vascular injury. Salmonella typhus vaccination was used as a model of acute systemic inflammation. In a double-blind randomized crossover study, 12 healthy volunteers received S. typhus vaccination or placebo. Phenotypic EPC populations enumerated by flow cytometry [CD34+VEGF receptor (VEGF)R-2+CD133+, CD14+VEGFR-2+Tie2+, CD45−CD34+, as a surrogate for late outgrowth EPCs, and CD34+CXCR-4+], EC-CFUs, and serum cytokine concentrations (high sensitivity C-reactive protein, IL-6, and stromal-derived factor-1) were quantified during the first 7 days. Vaccination increased circulating leukocyte (9.8 ± 0.6 vs. 5.1 ± 0.2 × 109cells/l, P < 0.0001), serum IL-6 [0.95 (0–1.7) vs. 0 (0–0) ng/l, P = 0.016], and VEGF-A [60 (45–94) vs. 43 (21–64) pg/l, P = 0.006] concentrations at 6 h and serum high sensitivity C-reactive protein at 24 h [2.7 (1.4–3.6) vs. 0.4 (0.2–0.8) mg/l, P = 0.037]. Vaccination caused a 56.7 ± 7.6% increase in CD14+cells at 6 h ( P < 0.001) and a 22.4 ± 6.9% increase in CD34+cells at 7 days ( P = 0.04). EC-CFUs, putative vascular progenitors, and the serum stromal-derived factor-1 concentration were unaffected throughout the study period ( P > 0.05 for all). In conclusion, acute systemic inflammation causes nonspecific mobilization of hematopoietic progenitor cells, although it does not selectively mobilize putative vascular progenitors. We suggest that systemic inflammation is not the primary stimulus for EPC mobilization after acute vascular injury.

Traditional EPC populations, CD34(+)VEGFR-2(+) and CD34(+)VEGFR-2(+)CD133(+) are not related to the extent of CAD or clinical outcome. However, CD34(+)CD45(-) cells are increased in patients with CAD and predict future cardiovascular events. It is likely that CD34(+)CD45(-) concentrations reflect the extent of vascular injury and atheroma burden.

ObjectiveCirculating CD34+CD45− cell concentrations are increased in patients with coronary artery disease, however their pathophysiological significance is unknown. We determined CD34+CD45− cell concentrations following percutaneous coronary intervention (PCI) in order to explore their role in acute vascular injury.MethodsIn a prospective time-course analysis, we quantified using flow cytometry circulating CD34+CD45− cells, traditional CD34+VEGFR-2+ putative endothelial progenitor cells (EPCs), CD14+ VEGFR− 2+Tie-2+ angiogenic monocytes and intercellular adhesion molecule expression (CXCR-4 and CD18) in patients, before and during the first week following diagnostic angiography (n=13) or PCI (n=23). Vascular endothelial growth factor-A (VEGF-A) and C reactive protein (CRP) were quantified by ELISA.ResultsUnlike diagnostic angiography, PCI increased circulating neutrophil and CRP concentrations at 24 and 48 h, respectively (p<0.002 for both). CD34+CD45− cell concentrations were unaffected by angiography (p>0.4), but were transiently increased 6 h following PCI (median (IQR) 0.93 (0.43–1.49) vs 1.51 (0.96–2.15)×106 cells/L; p=0.01), returning to normal by 24 h.This occurred in the absence of any change in serum VEFG-A concentration, adhesion molecule expression on CD34+ cells, or mobilisation of traditional EPCs or angiogenic monocytes (p>0.1 for all).ConclusionsPCI transiently increases circulating CD34+CD45− cells, without increasing CD34+ adhesion molecule expression or VEGF-A concentrations, suggesting that CD34+CD45− cells may be mobilised from the vessel wall directly as a result of mechanical injury. Traditional putative EPC and angiogenic monocytes are unaffected by PCI, and are unlikely to be important in the acute response to vascular injury.

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