Interplay of hypoxia, angiogenesis, and macrophages in pulp and periapical lesions: an immunohistochemical cross-sectional study

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.