A disintegrin‐like and metalloproteinase with thrombospondin‐1 (ADAMTS‐1) levels in gingival crevicular fluid correlate with vascular endothelial growth factor‐A, hypoxia‐inducible factor‐1α, and clinical parameters in patients with advanced periodontitis

Abstract

Background ADAMTS (a disintegrin‐like and metalloproteinase with thrombospondin) are a family of proteinases that are structurally similar to the family of matrix metalloproteinases with critical roles in damage and repair of the extracellular matrix. Their functions are closely related to inflammation, hypoxia, and vascularization. Our aim was to determine levels of ADAMTS‐1 in gingival crevicular fluid (GCF) in patients with advanced periodontal diseases and identify their association with hypoxia‐inducible factor‐1alpha (HIF‐1α), vascular endothelial growth factor (VEGF‐A), and clinical parameters of periodontitis. Methods The study consisted of three groups: healthy individuals (control; n = 20), generalized chronic periodontitis (CP; n = 21), and generalized aggressive periodontitis (GAgP; n = 20). Clinical parameters were measured. Levels of ADAMTS‐1, VEGF‐A, and HIF‐1α in GCF and serum were quantified by enzyme‐linked immunosorbent assay (ELISA) and reported as total amounts and concentration. Results ADAMTS‐1 total amount in GCF were significantly higher in patients with CP and GAgP compared with healthy individuals (P < 0.05). HIF‐1α total amount in GCF were also higher in periodontitis groups compared with the control group (P < 0.05). GCF total VEGF‐A content was significantly higher in the GAgP group compared with the CP and the controls (respectively; P = 0.023, P = 0.003). There was a significant correlation between ADAMTS‐1, VEGF‐A, and HIF‐1α levels in the GCF and clinical periodontal parameters (probing depth [PD], bleeding on probing [BOP], and clinical attachment loss (CAL); P < 0.05). Conclusion ADAMTS‐1 may play a role in advanced periodontal disease pathogenesis in correlation with tissue hypoxia and vascularization.

Effect of non‐surgical periodontal treatment on gingival crevicular fluid hypoxia inducible factor‐1 alpha, vascular endothelial growth factor and tumor necrosis factor‐alpha levels in generalized aggressive periodontitis patients

“…HIF‐1α protein expression was found to be markedly increased in chronically inflamed gingiva adjacent to periodontal pockets in patients with periodontitis 18,19 . GCF HIF‐1α levels were higher in G‐AgP patients compared to those of periodontally healthy individuals 20,21 . In consistent with the findings from these studies, 20,21 increased GCF HIF‐1α levels in G‐AgP group might suggest involvement of HIF‐1α with increased gingival inflammation and deeper periodontal pockets in those patients.…”

“…have reported that G‐AgP and chronic periodontitis patients had significantly higher GCF HIF‐1α levels than periodontally healthy controls. These findings suggest a possible association of HIF‐1α with the pathophysiology of periodontal inflammation 18‐21 . As HIF‐1α, under hypoxic condition, upregulates primer angiogenic mediator vascular endothelial growth factor (VEGF) 22,23 which is closely related to periodontal inflammation, wound healing and alveolar bone remodeling, 24‐26 TNF‐α increases HIF‐1α and its downstream effector VEGF in an oxygen‐independent manner 27,28 .…”

“…17 Increased HIF-1 protein expression levels have been shown in the gingival tissue of patients with periodontitis. 18,19 Recently, two clinical studies by Afacan et al 20 and Tayman et al 21 have reported that G-AgP and chronic periodontitis patients had significantly higher GCF HIF-1 levels than periodontally healthy controls. These findings suggest a possible association of HIF-1 with the pathophysiology of periodontal inflammation.…”

“…These findings suggest a possible association of HIF-1 with the pathophysiology of periodontal inflammation. [18][19][20][21] As HIF-1 , under hypoxic condition, upregulates primer angiogenic mediator vascular endothelial growth factor (VEGF) 22,23 which is closely related to periodontal inflammation, wound healing and alveolar bone remodeling, [24][25][26] TNF-increases HIF-1 and its downstream effector VEGF in an oxygenindependent manner. 27,28 It has been reported that protein expressions and GCF total amounts of HIF-1 may be associated with VEGF and TNF-levels in patients with periodontitis, which in turn implies that TNF-/HIF-1 /VEGF pathway may involved in periodontal inflammation.…”

“…Recently, two clinical studies by Afacan et al 20 . and Tayman et al 21 . have reported that G‐AgP and chronic periodontitis patients had significantly higher GCF HIF‐1α levels than periodontally healthy controls.…”