Immunoexpression of HIF-1α and VEGF in Periodontal Disease and Healthy Gingival Tissues

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.

RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells

“…However, our research showed that hypoxia markedly promoted tube formation and induced cell migration and that hypoxia stabilized HIF-1α and induced the expression of VEGF. HIF-1α also increases VEGF expression (28). Therefore, a possible explanation would be that these factors enhanced angiogenesis and cell migration, while EndMT partially offset the effects.…”

Morphometric and histopathological evaluation of the effect of grape seed proanthocyanidin on alveolar bone loss in experimental diabetes and periodontitis

“…Furthermore, hypoxia increased NF‐.B and HIF‐1α expressions in periodontal inflammation . Vasconcelos et al also showed that HIF‐1α and vascular endothelial growth factor (VEGF) synthesis increased in periodontitis compared to gingivitis and healthy gingiva. Yu et al also suggested that hypoxia and lack of oxygen in periodontal tissues might promote periodontitis by increasing receptor activator of NF‐.B ligand expression while decreasing osteoprotegerin expression in periodontal ligament cells.…”

Lymphatic growth factors are expressed in human gingiva and upregulated in gingival fibroblasts after stimulation

“…We therefore, test the hypothesis that GFs produce these growth factors upon inflammatory stimulation. Furthermore, VEGF‐A expression has been seen in endothelial and inflammatory cells, as well as in fibroblasts in human gingiva, whereas VEGF‐C and ‐D have never been described. Therefore, we also aim to investigate the expression of VEGF‐C and ‐D and the localization of their main receptor VEGFR‐3 in human gingiva.…”