Periodontitis as an inflammatory trigger in hypertension: From basic immunology to clinical implications

Abstract

Hypertension and periodontitis are both highly prevalent co-morbidities worldwide, and their occurrence increases with age. Multiple observational epidemiological studies have shown that periodontitis is associated with an increased cardiovascular disease (CVD) occurrence. Large systematic reviews and metanalyses further show that periodontitis increases the risk of hypertension and is associated with increased systolic and diastolic blood pressure. Genetic and clinical evidence, utilizing mendelian randomization and randomized clinical trials, support the causal role of periodontitis in hypertension. The mechanisms of this link remain unclear. Critical components of immune and inflammatory pathogenesis of periodontitis considerably overlap with immune mechanisms of hypertension. Clinical studies support that both C-reactive protein (CRP) levels and white blood cell counts (WBC) mediate the relationship between periodontal disease and high blood pressure. In particular, activation of Th1, Th17, T regulatory cells, and proinflammatory monocytes has been shown to be essential in both conditions. Immunosenescent dysregulated CD28null T cells have been implicated, along with key effector cytokines such as interleukin 6 (IL-6), TNF-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin 17 (IL-17). A better understanding of the relationships between hypertension and periodontitis is essential not only for possible utilization of this knowledge for a non-pharmacological approach to improving blood pressure control. It may also provide valuable pathogenetic clues linking inflammation and hypertension, which has become particularly relevant in the light of links between hypertension and autoimmune disorders or, more recently, COVID-19.

Armed to the Teeth—The Oral Mucosa Immunity System and Microbiota

“…Most studies have focused mainly on T cell populations, especially CD4+ and CD8+, which have been shown to be key mediators in periodontal disease [ 90 , 91 ]. Gingival CD4+ and CD8+ T cell populations produce effector cytokines IFNγ and IL-17 [ 86 , 92 ].…”

mTOR Signaling in the Regulation of CD4+ T Cell Subsets in Periodontal Diseases

“…Historically, it was believed that periodontitis is caused by specific bacterial infections and that people are unanimously susceptible to these infections and to the damage caused by them ( 13 ). Chronic inflammatory periodontal diseases are induced by imbalanced microbial communities which are presented in the form of subgingival dental plaques.…”

“…Nowadays, it has been accepted that the pathogenesis of periodontitis is more complex than the presence of virulent microorganisms ( 13 ). The microbes associated with periodontitis progressively destroy the periodontal tissues by producing numerous detrimental cytokines and virulence factors including exotoxins, endotoxins, fimbriae, capsule, and metabolic products ( 26 ).…”

“…smoking) and non-modifiable risk factors (eg. genetic inheritance and immune response) are critical etiologic agents in periodontal disease ( 13 ).…”

“…The final stage is the advanced lesion, which is characterized by irreversible attachment loss and bone loss ( 10 ). T cells play an important role in this process of the immune response, regulating the polyclonal activation of the B cells ( 11 ), inducing osteoclastogenesis via RANKL activation, and producing several periodontitis-associated cytokines, such as IFN-γ, TNF-α, and interleukin (IL)-17 ( 12 , 13 ).…”