PMID- 22704605
OWN - NLM
STAT- MEDLINE
DCOM- 20130104
LR  - 20121016
IS  - 1878-0539 (Electronic)
IS  - 1748-6815 (Linking)
VI  - 65
IP  - 11
DP  - 2012 Nov
TI  - EPO reverses defective wound repair in hypercholesterolaemic mice by increasing 
      functional angiogenesis.
PG  - 1559-68
LID - S1748-6815(12)00272-0 [pii]
LID - 10.1016/j.bjps.2012.05.006 [doi]
AB  - 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((R)) 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 Uml(-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.
CI  - Copyright (c) 2012 British Association of Plastic, Reconstructive and Aesthetic 
      Surgeons. Published by Elsevier Ltd. All rights reserved.
FAU - Elsherbiny, Ahmed
AU  - Elsherbiny A
AD  - Division of Plastic and Reconstructive Surgery, Department of Surgery, University 
      Hospital Zurich, CH-8091 Zurich, Switzerland.
FAU - Hogger, Dominik C
AU  - Hogger DC
FAU - Borozadi, Meisam Khorrami
AU  - Borozadi MK
FAU - Schmidt, Christian A
AU  - Schmidt CA
FAU - Plock, Jan
AU  - Plock J
FAU - Largo, Rene D
AU  - Largo RD
FAU - Lindenblatt, Nicole
AU  - Lindenblatt N
FAU - Giovanoli, Pietro
AU  - Giovanoli P
FAU - Contaldo, Claudio
AU  - Contaldo C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120615
PL  - Netherlands
TA  - J Plast Reconstr Aesthet Surg
JT  - Journal of plastic, reconstructive & aesthetic surgery : JPRAS
JID - 101264239
RN  - 0 (Recombinant Proteins)
RN  - 0 (epoetin beta)
RN  - 11096-26-7 (Erythropoietin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Erythropoietin/*pharmacology
MH  - Immunoenzyme Techniques
MH  - Mice
MH  - Microcirculation/*drug effects
MH  - Microscopy, Electron, Scanning
MH  - Microscopy, Fluorescence
MH  - Neovascularization, Physiologic/*drug effects
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Wound Healing/*drug effects
MH  - X-Ray Microtomography
EDAT- 2012/06/19 06:00
MHDA- 2013/01/05 06:00
CRDT- 2012/06/19 06:00
PHST- 2012/03/06 00:00 [received]
PHST- 2012/04/17 00:00 [revised]
PHST- 2012/05/06 00:00 [accepted]
PHST- 2012/06/19 06:00 [entrez]
PHST- 2012/06/19 06:00 [pubmed]
PHST- 2013/01/05 06:00 [medline]
AID - S1748-6815(12)00272-0 [pii]
AID - 10.1016/j.bjps.2012.05.006 [doi]
PST - ppublish
SO  - J Plast Reconstr Aesthet Surg. 2012 Nov;65(11):1559-68. doi: 
      10.1016/j.bjps.2012.05.006. Epub 2012 Jun 15.