All-trans retinoic acid improves the viability of ischemic skin flaps in diabetic rat models.

Abstract

AIMS: Endothelial progenitor cells (EPCs) play a critical role in neovascularization, which enhances proliferation under all-trans retinoic acid (ATRA) treatment. However, the effects of ATRA on the skin flap survival in diabetic flap ischemia remains unknown. METHODS: Ischemic random skin flaps were made in 40 diabetic Sprague-Dawley rats with 20 normal rats used as control in this study. At 7 days postoperatively, the surviving area of each skin flap was measured. Immunofluorescence staining was used to analyze capillary density and EPCs recruited to the flaps. The expression of ANG2 and VEGF was determined by Western blotting. Circulating EPC number was determined by flow cytometry. In vitro tube formation experiment was used to analyze the function of EPCs. RESULTS: The flap survival rate and capillary density of ATRA-treated flap were significantly increased. Fluorescence-activated cell sorting (FACS) analysis demonstrated a marked increase in systemic CD34+/Flk-1+ EPCs in ATRA-treated rat. The expression of ANG2 and VEGF was increased in diabetic flap tissues under ATRA administration. Furthermore, ATRA administration restored the impaired function of diabetic EPCs in tube formation. CONCLUSION: ATRA could notably exert preventive effects against skin flap necrosis and promote neovascularization in diabetic rats, which may partially through elevating the expression of ANG2 and VEGF, and augmenting EPC mobilization.