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Radial pressure waves mediate apoptosis and functional angiogenesis during wound repair in ApoE deficient mice


Contaldo, Claudio; Högger, Dominik C; Khorrami Borozadi, Meisam; Stotz, Michael; Platz, Uwe; Forster, Natasha; Lindenblatt, Nicole; Giovanoli, Pietro (2012). Radial pressure waves mediate apoptosis and functional angiogenesis during wound repair in ApoE deficient mice. Microvascular Research, 84(1):24-33.

Abstract

This study aims to quantify by intravital microscopy and histological wound scoring the effect of radial pressure wave treatment (RPWT) on murine incisional wound healing. The dorsal skinfold chamber in mice was used for intravital microscopy, whereby an incisional wound was created within the chamber. RPWT to the wound was carried out using a ballistic pressure wave source (EMS Swiss DolorClast). Animals received a dose of 500 pulses at an energy flux rate of 0.1mJ/mm(2) and a frequency of 3Hz at day 1, 3, 5, 7, 9, and 11 post wounding. RPW treated and untreated ApoE depleted mice (ApoE(-/-)) were compared to normal healing wild type animals (WT). The microcirculation of the wound was analyzed quantitatively in vivo using epi-illumination intravital fluorescence microscopy. Tissue samples were examined ex vivo for wound scoring and immunohistochemistry. Upon RPWT total wound score in ApoE(-/-) mice was increased by 13% (not significant) on day 3, by 37% on day 7 (P<0.05), and by 39% on day 13 (P<0.05) when compared to untreated ApoE(-/-) mice. Improved wound healing was associated with an increase of functional angiogenetic density by 23% (not significant) on day 5, by 36% on day 7 (P<0.05), and by 41% on day 9 (P<0.05). Following RPWT, on day three we observed enhanced expression of capase-3 (2-fold), proliferating cell nuclear antibody (PCNA, 1,6-fold), and endothelial nitric oxide synthase (eNOS, 2.6-fold), all P<0.05. In conclusion repetitive RPWT accelerated wound healing in ApoE(-/-) mice by increasing functional neovascular density. In addition our findings strongly suggest that RPW may facilitate the linear progression of wound healing phases by fostering apoptosis.

Abstract

This study aims to quantify by intravital microscopy and histological wound scoring the effect of radial pressure wave treatment (RPWT) on murine incisional wound healing. The dorsal skinfold chamber in mice was used for intravital microscopy, whereby an incisional wound was created within the chamber. RPWT to the wound was carried out using a ballistic pressure wave source (EMS Swiss DolorClast). Animals received a dose of 500 pulses at an energy flux rate of 0.1mJ/mm(2) and a frequency of 3Hz at day 1, 3, 5, 7, 9, and 11 post wounding. RPW treated and untreated ApoE depleted mice (ApoE(-/-)) were compared to normal healing wild type animals (WT). The microcirculation of the wound was analyzed quantitatively in vivo using epi-illumination intravital fluorescence microscopy. Tissue samples were examined ex vivo for wound scoring and immunohistochemistry. Upon RPWT total wound score in ApoE(-/-) mice was increased by 13% (not significant) on day 3, by 37% on day 7 (P<0.05), and by 39% on day 13 (P<0.05) when compared to untreated ApoE(-/-) mice. Improved wound healing was associated with an increase of functional angiogenetic density by 23% (not significant) on day 5, by 36% on day 7 (P<0.05), and by 41% on day 9 (P<0.05). Following RPWT, on day three we observed enhanced expression of capase-3 (2-fold), proliferating cell nuclear antibody (PCNA, 1,6-fold), and endothelial nitric oxide synthase (eNOS, 2.6-fold), all P<0.05. In conclusion repetitive RPWT accelerated wound healing in ApoE(-/-) mice by increasing functional neovascular density. In addition our findings strongly suggest that RPW may facilitate the linear progression of wound healing phases by fostering apoptosis.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
04 Faculty of Medicine > University Hospital Zurich > Clinic for Reconstructive Surgery
Dewey Decimal Classification:610 Medicine & health
Language:German
Date:July 2012
Deposited On:18 Feb 2013 12:22
Last Modified:07 Dec 2017 19:24
Publisher:Elsevier
ISSN:0026-2862
Publisher DOI:https://doi.org/10.1016/j.mvr.2012.03.006
PubMed ID:22504489

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