Objective., Erythropoietin interacts with vascular endothelial growth factor (VEGF) and stimulates endothelial cell mitosis and motility; thus it may be of importance in the complex phenomenon of wound healing. The purpose of this study was to investigate the effect of recombinant human erythropoietin (rHuEPO) on experimental bum wounds. Design: Randomized experiment. Setting. Research laboratory. Subjects. C57BL/6 male mice weighing 25-30 g. Interventions. Mice were immersed in 80 degrees C water for 10 secs to achieve a deep-dermal second degree burn. Animals were randomized to receive either rHuEPO (400 units/kg/day for 14 days in 100 mu L subcutaneously) or its vehicle alone (100 mu l/day distilled water for 14 days subcutaneously). On day 14 the animals were killed. Burn areas were used for histologic examination, evaluation of neoangiogenesis by immunohistochemistry, and expression (Western blot) of the specific endothelial marker CD31 as well as quantification of microvessel density, measurement of VEGF wound content (enzyme-linked immunosorbent assay), expression (Western blot) of endothelial and inducible nitric oxide synthases, and determination of wound nitric oxide (NO) products. Measurements and Main Results. rHuEPO increased burn wound reepithelialization and reduced the time to final wound closure. These effects were completely abated by a passive immunization with specific antibodies against erythropoietin. rHuEPO improved healing of burn wound through increased epithelial proliferation, maturation of the extracellular matrix, and angiogenesis. The hematopoietic factor augmented neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of the specific endothelial marker CD31. Furthermore, rHuEPO enhanced the wound content of VEGF caused a marked expression of endothelial and inducible nitric oxide synthases and increased wound content of nitric oxide products. Conclusions: Our study suggests that rHuEPO may be an effective therapeutic approach to improve clinical outcomes after thermal injury.

Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds / M., Galeano; D., Altavilla; A., Bitto; L., Minutoli; M., Calo; P., Lo Cascio; F., Polito; G., Giugliano; G., Squadrito; Mioni, Chiara; Giuliani, Daniela; F. S., Venuti; F., Squadrito. - In: CRITICAL CARE MEDICINE. - ISSN 0090-3493. - STAMPA. - 34(2006), pp. 1139-1146.

Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds

MIONI, Chiara;GIULIANI, Daniela;
2006

Abstract

Objective., Erythropoietin interacts with vascular endothelial growth factor (VEGF) and stimulates endothelial cell mitosis and motility; thus it may be of importance in the complex phenomenon of wound healing. The purpose of this study was to investigate the effect of recombinant human erythropoietin (rHuEPO) on experimental bum wounds. Design: Randomized experiment. Setting. Research laboratory. Subjects. C57BL/6 male mice weighing 25-30 g. Interventions. Mice were immersed in 80 degrees C water for 10 secs to achieve a deep-dermal second degree burn. Animals were randomized to receive either rHuEPO (400 units/kg/day for 14 days in 100 mu L subcutaneously) or its vehicle alone (100 mu l/day distilled water for 14 days subcutaneously). On day 14 the animals were killed. Burn areas were used for histologic examination, evaluation of neoangiogenesis by immunohistochemistry, and expression (Western blot) of the specific endothelial marker CD31 as well as quantification of microvessel density, measurement of VEGF wound content (enzyme-linked immunosorbent assay), expression (Western blot) of endothelial and inducible nitric oxide synthases, and determination of wound nitric oxide (NO) products. Measurements and Main Results. rHuEPO increased burn wound reepithelialization and reduced the time to final wound closure. These effects were completely abated by a passive immunization with specific antibodies against erythropoietin. rHuEPO improved healing of burn wound through increased epithelial proliferation, maturation of the extracellular matrix, and angiogenesis. The hematopoietic factor augmented neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of the specific endothelial marker CD31. Furthermore, rHuEPO enhanced the wound content of VEGF caused a marked expression of endothelial and inducible nitric oxide synthases and increased wound content of nitric oxide products. Conclusions: Our study suggests that rHuEPO may be an effective therapeutic approach to improve clinical outcomes after thermal injury.
34
1139
1146
Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds / M., Galeano; D., Altavilla; A., Bitto; L., Minutoli; M., Calo; P., Lo Cascio; F., Polito; G., Giugliano; G., Squadrito; Mioni, Chiara; Giuliani, Daniela; F. S., Venuti; F., Squadrito. - In: CRITICAL CARE MEDICINE. - ISSN 0090-3493. - STAMPA. - 34(2006), pp. 1139-1146.
M., Galeano; D., Altavilla; A., Bitto; L., Minutoli; M., Calo; P., Lo Cascio; F., Polito; G., Giugliano; G., Squadrito; Mioni, Chiara; Giuliani, Daniela; F. S., Venuti; F., Squadrito
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/304390
Citazioni
  • ???jsp.display-item.citation.pmc??? 29
  • Scopus 127
  • ???jsp.display-item.citation.isi??? 105
social impact