文摘
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Summary
This study aims to elucidate the effect of erythropoietin (EPO) on the microcirculation during wound healing in mice genetically depleted of apolipoprotein E (ApoE?/?). The skinfold chamber in mice was used for intravital microscopy, whereby an incisional wound was created within the chamber. Animals received Recormon? 1000 U kg?1 body weight (BW) intra-peritoneally (i.p.) at day 1, 3, 5, 7, 9 and 11 post-wounding at a concentration of 100 U ml?1 (n = 42). Normal healing and vehicle-treated wild type animals (WT) served as controls. The microcirculation of the wound was analysed quantitatively in?vivo using epi-illumination intravital fluorescence microscopy. Microtomography (micro-CT) analysis of casted wound microvessels was performed allowing three-dimensional (3D) histomorphometric analysis. Tissue samples were examined ex?vivo for wound scoring and for expression analysis of EPO-Receptor (Epo-R) and endothelial nitric oxide synthase (eNOS). Upon EPO treatment, the total wound score in ApoE?/? mice was increased by 23 % on day 3, by 26 % on day 7 and by 18 % on day 13 when compared to untreated ApoE?/? mice (all P < 0.05 vs. vehicle). Improved wound healing was accompanied with a significant increase of functional angiogenetic density and angiogenetic red blood cell perfusion on days 5, 7, 9 and 11 post-wounding. 3D histomorphometric analysis revealed an increase of vessel thickness (1.7-fold), vessel volume (2.4-fold) and vessel surface (1.7-fold) (all P < 0.05 vs. vehicle). In addition, improved wound healing was associated with enhanced Epo-R expression (4.6-fold on day 3 and 13.5-fold on day 7) and eNOS expression (2.4-fold on day 7) (all P < 0.05 vs. vehicle). Our data demonstrate that repetitive systemic EPO treatment reverses microvascular dysfunction during wound healing in hypercholesterolaemic mice by inducing new vessel formation and by providing the wound with more oxygen.
