Gingival crevicular fluid and salivary HIF-1α, VEGF, and TNF-α levels in periodontal health and disease

Abstract

Background: Hypoxia-inducible factor-1 alpha (HIF-1α) is expressed as an adaptive response to hypoxia, mediates angiogenesis through the expression of vascular endothelial growth factor (VEGF) and can be induced by tumor necrosis factor-alpha (TNF-α). This study aimed to investigate the gingival crevicular fluid (GCF) and salivary HIF-1α, VEGF, and TNF-α levels in periodontal health and disease.

Methods: A total of 87 individuals, 20 generalized aggressive periodontitis (G-AgP), 20 chronic periodontitis (CP), 26 gingivitis patients, and 21 periodontally healthy individuals, were included. Clinical periodontal parameters were recorded; GCF and salivary samples were collected; and HIF-1α, VEGF, and TNF-α levels were measured by enzyme-linked immunosorbent assay. Nonparametric tests were used for the statistical analyses.

Results: G-AgP and CP groups had significantly higher GCF HIF-1α, VEGF, and TNF-α total amounts than gingivitis and healthy groups (P < 0.05). GCF HIF-1α and TNF-α total amounts in gingivitis group were significantly higher than the healthy group (P < 0.05). GCF and salivary concentrations of biomarkers were similar in both periodontitis groups (P > 0.05). Salivary HIF-1α concentrations in gingivitis group were significantly higher than G-AgP and healthy groups (P < 0.05). GCF HIF-1α, VEGF, and TNF-α total amounts were positively correlated with the site-specific clinical periodontal parameters and with each other (P < 0.05).

Conclusions: HIF-1α is detectable in GCF and saliva of periodontally diseased and healthy individuals, and the GCF levels of the biomarker can be affected by disease status. Increased GCF HIF-1α, VEGF, and TNF-α levels in both chronic and aggressive form of periodontitis might suggest the role of TNF-α/HIF-1α/VEGF pathway in the pathogenesis of periodontal diseases.

Trial registration: ClinicalTrials.gov NCT03558906.

Keywords: cytokines; gingival crevicular fluid; periodontitis; saliva.