Correlational analysis of the regulatory interplay between molecules and cellular components mediating angiogenesis in wound healing under normal and hyperglycemic conditions
Affiliations: [a]
Bogomolets National Medical University, Kiev, Ukraine
| [b]
Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr University Bochum, Herne, Germany
Correspondence:
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Corresponding author: Larysa Natrus, MD, Professor, PhD of Medical Sciences, Head of Department of Modern Technologies Of Medical Diagnostics And Treatment, Bogomolets National Medical University, 34 Peremoha Avenue 03115, Kiev, Ukraine. E-mail: Lnatrus777@gmail.com. ORCID:0000-0002-0416-2600.
Abstract: AIM:The aim of this study was to correlate the content of cells with regulatory molecules associated with angiogenesis in wound healing in a rat model of hyperglycemia. We hypothesize that blood neutrophils are the main VEGF source and can stimulate FLT-1 receptor expression, which is the perquisite for efficient neoangiogenesis. MATERIALS AND METHODS:Kinetic studies of the healing dynamics (3, 7, 14, 21 days) of burn wounds on the skin were conducted in white adult male rats. The content of nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), its receptor (Flt-1) in the regenerated tissue was analyzed by western blot. Numbers of cells associated with the regenerative process and from peripheral blood (PB) were determined. Additionally a bone marrow (BM) myelogram was conducted. RESULTS:The relative number of peripheral blood (PB) neutrophils was found to be associated with the level of VEGF (R = 0.708) and Flt-1 (R = 0.472). The relative number of fibroblasts was also associated with VEGF (R = 0.562), but not with Flt-1. A negative association was found between the number of neutrophils in the regenerated tissue with VEGF (R = –0.454) and FLT-1 (R = –0.665). This confirms our hypothesis, that blood neutrophils are the main VEGF producer that stimulate the expression of the FLT-1 receptor subsequently inducing neoangiogenesis.Furthermore, that under hyperglycemic conditions fibroblasts were highly associated with VEGF (R = 0.800), while negatively associated with FLT-1 (R = –0.506). There was a high association between PB neutrophils and newly generated tissue cells: neutrophils (R = 0.717) and macrophages (R = 0.622), as well as the association between neutrophils and macrophages (R = 0.798). This is an indication of chronic inflammation and increased transmigration of blood cells to the burned tissue. CONCLUSION:Blood neutrophils are the main producer of VEGF and stimulate the expression of the FLT-1 receptor. In the context of hyperglycemia the imbalance of receptor and ligand associated with angiogenesis indicates for chronic inflammation: VEGF and FLT-1, which facilitates hypoxia, prevents the physiological course of burn wound healing and may be an important factor in impaired tissue regeneration in diabetes.
