title: Recombinant human erythropoietin stimulates angiogenesis and healing of ischemic skin wounds.
abstract: Wound healing in ischemic tissues such as flap margins due to inadequate blood supply is still a source of considerable morbidity in surgical practice. Adequate tissue perfusion is particularly important in wound healing. We investigated the effects of recombinant human erythropoietin (rHuEPO) on wound healing in an ischemic skin wound model. Sixty-three Sprague-Dawley rats were used. Normal incisional wound and H-shaped double flaps were used as the wound models. Animals were treated with rHuEPO (400 IU/kg) or its vehicle. Rats were killed on different days (3, 5, and 10 days after skin injury) and the wounded skin tissues were used for immunohistochemistry and for analysis of vascular endothelial growth factor content and collagen content. Tissue transglutaminase immunostaining of histological specimens was used as a vascular marker to determine the level of microvessel density. The results showed a higher level of vascular endothelial growth factor protein and an increased microvessel density in ischemic wounds with rHuEPO treatment than the normal incisional wounds and ischemic control wounds. Collagen content was higher in the incisional wounds and in the ischemic wounds with rHuEPO treatment compared with the ischemic control wounds. Our results suggest that erythropoietin may be an effective therapeutic approach in improving healing in ischemic skin wounds.
authors.affiliation: Department of Internal Medicine, University of Messina, Messina, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Buemi
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Galeano
authors.forename: Alessio
authors.initials: A
authors.lastname: Sturiale
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ientile
authors.forename: Costantino
authors.initials: C
authors.lastname: Crisafulli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Parisi
authors.forename: MariaAntonietta
authors.initials: M
authors.lastname: Catania
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Calapai
authors.forename: Patrizia
authors.initials: P
authors.lastname: Impalà
authors.forename: Carmela
authors.initials: C
authors.lastname: Aloisi
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tuccari
authors.forename: Nicola
authors.initials: N
authors.lastname: Frisina
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology; D004921:Erythropoietin / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000737:chemistry; D007150:Immunohistochemistry; D007511:Ischemia; D008297:Male; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012867:Skin / Q000473:pathology*; D013997:Time Factors; D011503:Transglutaminases / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D003094:Collagen; D011503:Transglutaminases; D006909:Hydroxyproline