Ischemia-induced bone marrow-derived endothelial progenitor cells mobilization impairment in diabetic mice / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To determine whether ischemia-induced bone marrow-derived EPCs mobilization is impaired in diabetic mice and the association with vascular endothelial growth factor (VEGF) release post ischemia.</p><p><b>METHODS</b>C57Bl/6 mice were injected with 40 mg x kg(-1) x d(-1) streptozotocin for 5 days to induce diabetes and mice with fasting glucose > 10 mmol/L were included to DM group, control mice were injected with placebo. Two months later, hindlimb ischemia was induced by left femoral artery dissection and ligation. The ischemia was visualized by tetrazolium dye staining and pre-mortem angiography. The percentage of c-Kit(+)/Sca-1(+)/flk-1(+) early EPCs in peripheral blood mononuclear cells (PBMCs) was detected by flow cytometric analysis on days 0 (pre-ligation), 1, 3, 5, 7 and 14 days post-ligation. The plasma VEGF level was measured with a standardized ELISA-Kit.</p><p><b>RESULTS</b>Circulating EPCs number was significantly lower in diabetic mice than that in control mice (0.60% +/- 0.03% vs. 0.95% +/- 0.09%, P < 0.001) and the plasma VEGF was undetectable in all animals before ligation Similar EPCs kinetics following induction of hindlimb ischemia were shown in both groups. However, EPCs mobilization was significantly impaired in diabetic mice compared with control mice within 3 days post ischemia (day 1 1.16% +/- 0.20% vs. 1.80% +/- 0.32%, P < 0.05; day 3 1.38% +/- 0.34% vs. 2.37% +/- 0.52%, P < 0.05). In parallel, plasma VEGF increase post ischemia was significantly less in diabetic mice than that in control mice (day 1 73.1 pg/ml +/- 18.6 pg/ml vs. 128.5 pg/ml +/- 44.2 pg/ml, P < 0.05).</p><p><b>CONCLUSION</b>Our data suggest that ischemia-induced bone marrow-derived EPCs mobilization is impaired in diabetic mice, which may be related to the insufficient release of plasma VEGF post ischemia.</p>