Quan Yuan1,2, Andreas Arkudas1, Raymund E Horch1, Matthias Hammon3, Oliver Bleiziffer1,4, Michael Uder3, Hannes Seuss3. 1. 1 Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University , Erlangen-Nuernberg (FAU), Erlangen, Germany . 2. 2 Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China . 3. 3 Department of Radiology, University Hospital Erlangen, Friedrich Alexander University , Erlangen-Nuernberg (FAU), Erlangen, Germany . 4. 4 Department of Plastic and Hand Surgery, Inselspital Bern, Universität Bern , Bern, Switzerland .
Abstract
INTRODUCTION: The aim of this study was to analyze the three-dimensional distribution of hypoxia in the arteriovenous (AV) loop model in rats, by examining the distribution of hypoxia-inducible factor-1 alpha (HIF-1α). MATERIALS AND METHODS: AV loops were created from the femoral artery and vein of male Lewis rats and an interpositional graft from the contralateral femoral vein. This AV fistula was embedded in a fibrin-filled isolation chamber and subcutaneously implanted into the thigh. The specimens were harvested after 7 days (n = 4), 10 days (n = 5), and 14 days (n = 4). The fibrin clots were stained for lectin, HIF-1α, and ectodysplasin 1 (ED1). The distribution of positive and negative cells was analyzed in three dimensions and at different points in time. RESULTS: The HIF-1α-positive rate increased from the proximity of the central vessel to the distant regions. From day 7 to 10, we noted a decrease in the HIF-1α-positive rate in the proximity of the vessels and an increase in the periphery. A global decrease in positive cells was seen at day 14. HIF-1α and macrophage (ED1) double staining indicated that macrophages accounted for a significant fraction of the cells. Double staining for endothelium (with lectin) demonstrated that no HIF-1α was detectable in well-vascularized areas. CONCLUSION: In the AV loop model, the HIF-1α-positive cell distribution is highly related to the vascularization process. The onset of rapid vessel outgrowth follows the increase of the HIF-1α rate closely, indicating that HIF-1α may be a driving force for vascularization.
INTRODUCTION: The aim of this study was to analyze the three-dimensional distribution of hypoxia in the arteriovenous (AV) loop model in rats, by examining the distribution of hypoxia-inducible factor-1 alpha (HIF-1α). MATERIALS AND METHODS: AV loops were created from the femoral artery and vein of male Lewis rats and an interpositional graft from the contralateral femoral vein. This AV fistula was embedded in a fibrin-filled isolation chamber and subcutaneously implanted into the thigh. The specimens were harvested after 7 days (n = 4), 10 days (n = 5), and 14 days (n = 4). The fibrin clots were stained for lectin, HIF-1α, and ectodysplasin 1 (ED1). The distribution of positive and negative cells was analyzed in three dimensions and at different points in time. RESULTS: The HIF-1α-positive rate increased from the proximity of the central vessel to the distant regions. From day 7 to 10, we noted a decrease in the HIF-1α-positive rate in the proximity of the vessels and an increase in the periphery. A global decrease in positive cells was seen at day 14. HIF-1α and macrophage (ED1) double staining indicated that macrophages accounted for a significant fraction of the cells. Double staining for endothelium (with lectin) demonstrated that no HIF-1α was detectable in well-vascularized areas. CONCLUSION: In the AV loop model, the HIF-1α-positive cell distribution is highly related to the vascularization process. The onset of rapid vessel outgrowth follows the increase of the HIF-1α rate closely, indicating that HIF-1α may be a driving force for vascularization.
Authors: Rafael G Jakubietz; Danni F Jakubietz; Raymund E Horch; Joerg G Gruenert; Rainer H Meffert; Michael G Jakubietz Journal: Plast Reconstr Surg Glob Open Date: 2019-09-30