Hypoxic Responses in Periodontal Tissues: Influence of Smoking and Periodontitis

J Clin Periodontol. 2025 Feb;52(2):249-257. doi: 10.1111/jcpe.14087. Epub 2024 Nov 3.

Abstract

Aim: This study aimed to investigate the hypoxic changes in periodontal tissues resulting from smoking and periodontitis by assessing levels of hypoxia-inducible factors (HIF-1α, HIF-2α, HIF-3α) and vascular endothelial growth factor (VEGF) in gingival crevicular fluid (GCF).

Materials and methods: The study comprised 22 periodontally healthy non-smokers (Group H), 22 periodontally healthy smokers (Group HS), 22 non-smokers with periodontitis (Group P) and 22 smokers with periodontitis (Group PS). Clinical periodontal parameters were documented, and GCF samples were collected and analysed using enzyme-linked immunosorbent assay (ELISA).

Results: Significantly elevated levels of HIF-1α, HIF-3α and VEGF were observed in Groups HS, P and PS compared to Group H (p < 0.05). Moreover, higher HIF-2α levels were detected in the Groups HS and P compared to Group H (p < 0.05). Significant correlations were detected between all evaluated hypoxia biomarkers in the Group P (p < 0.05) except HIF-2α and HIF-3α. However, in the PS group, significant correlation appeared only between HIF-1α and HIF-2α (p < 0.05).

Conclusion: Our findings indicate that smoking and periodontitis induce comparable hypoxic effects in periodontal tissues, as evidenced by the evaluated biomarkers. Further research is warranted to gain a deeper understanding of the mechanisms underlying hypoxia in periodontal tissues.

Keywords: gingival crevicular fluid; hypoxia; hypoxia‐inducible factor 1; periodontitis; smoking; vascular endothelial growth factor.

MeSH terms

  • Adult
  • Apoptosis Regulatory Proteins
  • Basic Helix-Loop-Helix Transcription Factors / analysis
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gingival Crevicular Fluid / chemistry
  • Humans
  • Hypoxia* / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / analysis
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • Middle Aged
  • Periodontitis* / metabolism
  • Periodontium* / metabolism
  • Repressor Proteins
  • Smoking* / adverse effects
  • Smoking* / metabolism
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Vascular Endothelial Growth Factor A
  • endothelial PAS domain-containing protein 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Biomarkers
  • HIF3A protein, human
  • HIF1A protein, human
  • Repressor Proteins
  • Apoptosis Regulatory Proteins