Restorative Dentistry & Endodontics

Research Article

Interplay of hypoxia, angiogenesis, and macrophages in pulp and periapical lesions: an immunohistochemical cross-sectional study: Puja Chatterjee, Mala Kamboj, Shweta Mittal, Anjali Narwal, Anju Devi; J Korean Acad Conserv Dent ;Published online April 23, 2026; DOI: https://doi.org/10.5395/rde.2026.51.e22 [Epub ahead of print]

Abstract PDF PubReader ePub: Objectives
This study evaluated and correlated the immune expression of hypoxia and angiogenesis with macrophages in periapical granuloma (PG), radicular cyst (RC), and healthy pulp (HP).
Methods
An observational study was performed on 51 tissue blocks equally divided among the groups, stained immunohistochemically for hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and CD68, and the mean expression was calculated. Data were analyzed using Kruskal-Wallis, Mann-Whitney, Spearman correlation tests (p < 0.001), and multiple linear regression analysis (p ≤ 0.05).
Results
HIF-1α expression was highest in PG than RC and HP (p < 0.001). Significant differences were found between HP, PG, and RC (both p < 0.001). VEGF expression was highest in RC than in PG and HP (p < 0.001), with significant differences between HP and both PG and RC (p < 0.001); pairwise comparisons were significant between all groups (p < 0.001, p < 0.001, p = 0.018). Correlation analysis showed significant correlations between VEGF and CD68 in HP and PG (p = 0.007 and p = 0.028, respectively). Linear regression showed that study groups were significantly associated with mean scores of HIF-1α, VEGF, and CD68 (p = 0.002, p = 0.001, p < 0.001).
Conclusions
HIF-1α, VEGF, and CD68 showed increased expression in PGs and RCs, suggesting an association between hypoxic conditions, enhanced angiogenic activity, and macrophage presence within the periapical inflammatory microenvironment. Future studies exploring HIF-1α and VEGF inhibitors as potential treatment modalities for periapical lesions are warranted.

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