Association between periodontitis and arterial hypertension: A systematic review and meta-analysis.

BACKGROUND: Several studies have shown that periodontal diseases are associated with hypertension (HT). However, heterogeneity among populations, diagnosis criteria, and shared risk factors represent some difficulties in terms of interpretation. Therefore, the aim of this study was to determine the magnitude of the association between periodontal diseases and HT. METHODS AND RESULTS: A systematic review and meta-analysis, including studies published up to June 2016, have been performed. Sixteen studies assessing the association between periodontal diseases and HT have been included. The meta-analysis considering all included studies (moderate to severe periodontitis) showed that the presence of HT was associated with the presence of periodontal diseases (OR, 1.50; 95% CI, 1.27-1.78). To reduce potential bias, a stratified analysis has been performed illustrating the impact of inclusion criteria and adjustments on the magnitude of the association. Interestingly, when only studies with secure diagnosis of severe periodontitis and HT were considered, an OR=1.64 (95% CI, 1.23-2.19) has been measured. CONCLUSIONS: Periodontal diseases are associated with a higher risk of HT especially for severe periodontitis. However, no conclusions could be made regarding the causative involvement of periodontal diseases mainly due to the reduced number of available prospective studies and remaining questions regarding underlying biological mechanisms.

Porphyromonas gingivalis Differentially Modulates Cell Death Profile in Ox-LDL and TNF-α Pre-Treated Endothelial Cells.

OBJECTIVE: Clinical studies demonstrated a potential link between atherosclerosis and periodontitis. Porphyromonas gingivalis (Pg), one of the main periodontal pathogen, has been associated to atheromatous plaque worsening. However, synergism between infection and other endothelial stressors such as oxidized-LDL or TNF-α especially on endothelial cell (EC) death has not been investigated. This study aims to assess the role of Pg on EC death in an inflammatory context and to determine potential molecular pathways involved. METHODS: Human umbilical vein ECs (HUVECs) were infected with Pg (MOI 100) or stimulated by its lipopolysaccharide (Pg-LPS) (1µg/ml) for 24 to 48 hours. Cell viability was measured with AlamarBlue test, type of cell death induced was assessed using Annexin V/propidium iodide staining. mRNA expression regarding caspase-1, -3, -9, Bcl-2, Bax-1 and Apaf-1 has been evaluated with RT-qPCR. Caspases enzymatic activity and concentration of APAF-1 protein were evaluated to confirm mRNA results. RESULTS: Pg infection and Pg-LPS stimulation induced EC death. A cumulative effect has been observed in Ox-LDL pre-treated ECs infected or stimulated. This effect was not observed in TNF-α pre-treated cells. Pg infection promotes EC necrosis, however, in infected Ox-LDL pre-treated ECs, apoptosis was promoted. This effect was not observed in TNF-α pre-treated cells highlighting specificity of molecular pathways activated. Regarding mRNA expression, Pg increased expression of pro-apoptotic genes including caspases-1,-3,-9, Bax-1 and decreased expression of anti-apoptotic Bcl-2. In Ox-LDL pre-treated ECs, Pg increased significantly the expression of Apaf-1. These results were confirmed at the protein level. CONCLUSION: This study contributes to demonstrate that Pg and its Pg-LPS could exacerbate Ox-LDL and TNF-α induced endothelial injury through increase of EC death. Interestingly, molecular pathways are differentially modulated by the infection in function of the pre-stimulation.