Recombinant human erythropoietin stimulates angiogenesis and healing of ischemic skin wounds.
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.
Buemi
Michele
M
Department of Internal Medicine, University of Messina, Messina, Italy.
Galeano
Mariarosaria
M
Sturiale
Alessio
A
Ientile
Riccardo
R
Crisafulli
Costantino
C
Parisi
Alessandra
A
Catania
MariaAntonietta
M
Calapai
Gioacchino
G
Impalà
Patrizia
P
Aloisi
Carmela
C
Squadrito
Francesco
F
Altavilla
Domenica
D
Bitto
Alessandra
A
Tuccari
Giovanni
G
Frisina
Nicola
N
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
D006454:Hemoglobins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D003094:Collagen; D011503:Transglutaminases; D006909:Hydroxyproline