Abstract

Hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) are proteins that stimulate the proliferation and migration of endothelial cells. These proteins have been described in many pathologic and inflammatory conditions, but their involvement in the development of periodontitis has not been thoroughly investigated. This study compared the immunohistochemical expression of these proteins, involved in angiogenesis and hypoxia, by immunostained inflammatory and endothelial cells in periodontal disease and healthy gingival tissues. Gingival tissue samples were divided as follows: 30 samples with chronic periodontitis, 30 with chronic gingivitis, and 30 of healthy gingiva. Results were analyzed statistically by the Kruskal-Wallis, Mann-Whitney and Spearman correlation tests (p=0.01). Inflammatory and endothelial cells were found to express these proteins. Periodontitis showed median percentage of HIF-1α-positive cells of 39.6%, 22.0% in cases of gingivitis and 0.9% in the healthy gingiva group (p=0.001). For VEGF, median percentage of immunopositive cells was 68.7% for periodontitis, 66.1% in cases for gingivitis, and 19.2% for healthy gingival specimens (p<0.001). Significant correlation between VEGF and HIF-1α was also observed in healthy gingiva (p<0.001).The increased expression of HIF-1α and VEGF in periodontitis, compared to gingivitis and healthy gingiva, suggests possible activation of the HIF-1α pathway in advanced periodontal disease. The correlation between HIF-1α and VEGF expression in healthy gingiva suggests a physiological function for these proteins in conditions of homeostasis. In periodontal disease, HIF-1α and VEGF expression may be regulated by other factors, in addition to hypoxia, such as bacterial endotoxins and inflammatory cytokines.

Highlights

  • Periodontal disease is a complex inflammatory condition that affects the tooth-supporting tissues, as a result of infection with anaerobic Gram-negative bacteria

  • The objective of the present study was to analyze the expression of these proteins in gingivitis, periodontitis and healthy gingiva in order to know if there is a higher immunoexpression of HIF-1α and vascular endothelial growth factor (VEGF) in diseased tissues and to have a better comprehension of these proteins on pathogenesis of periodontal diseases

  • The immunoexpressions of VEGF and HIF-1α were compared between groups using the nonparametric Kruskal-Wallis test

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Summary

Introduction

Periodontal disease is a complex inflammatory condition that affects the tooth-supporting tissues, as a result of infection with anaerobic Gram-negative bacteria. The infiltration of inflammatory cells causes endothelial damage and microcirculatory failure, resulting in decreased oxygen tension (4). This condition, as well as the activity of cytokines and growth factors such as TGF-α, TGF-β, PDGF, FGF, PGE, IL1, IL-6 and IL-8 and endotoxins, stimulates the production of vascular endothelial growth factor (VEGF), which is one of the most important proangiogenic factors (5). VEGF is secreted by mesenchymal cells and is recognized by specific receptors present on vascular endothelial cells (6) This factor possesses mitogenic activity, regulates endothelial cell migration and vascular permeability, and induces the expression of antiapoptotic proteins in these cells. VEGF is the most important factor involved in physiological and pathological neovascularization and an increased expression of this protein has been demonstrated in patients with periodontal disease (7,8)

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