Percutaneous coronary intervention causes a rapid but transient mobilisation of CD34(+)CD45(-) cells

Abstract

Objective: Circulating 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.

Methods: In 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.

Results: Unlike 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)×10(6) 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).

Conclusions: PCI 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.

Keywords: CORONARY ARTERY DISEASE.

Figure 1

Flow cytometric analysis of putative progenitor cells. Representative dot plots of negative controls and stained samples are shown in red and blue respectively. First, leucocytes were identified on the basis of their characteristic forward and side scatter profile (A). CD34-FITC (B and C) expression and the proportion of CD34⁺ events expressing CD18 (D and E) and CXCR-4 (F and G) were determined. Similarly CD133-PE⁺ (H and I), CD45-PercP⁺ (J and K), and VEGFR-2-APC⁺ (L and M) events were identified. Co-expression of surface markers was determined using Boolean principles. In separate analyses CD14-FITC⁺ events were identified (N), and those expressing Tie-2-APC and or VEGFR-2-PE were determined using quadrant analysis (O and P). Gates were set on single or unstained negative controls where appropriate.

Figure 2

Inflammatory response and CD34⁺CD45⁻ cell release following percutaneous coronary intervention (PCI). PCI rapidly but transiently mobilised CD34⁺CD45⁻ cells into the peripheral circulation, peaking at 6 h; p=0.01. Circulating concentrations had fallen back to baseline by 24 h. In contrast, the systemic inflammatory response caused by PCI was relatively prolonged, with CRP concentrations continuing to increase for at least 48 h; p=0.001. Diagnostic coronary angiography alone did not cause an inflammatory response or effect the CD34⁺CD45⁻ concentration; p>0.5 for all. Data are median and IQR.