Cardiovascular disease is the leading cause of death worldwide, and a number of risk factors have been identified including, but not limited to, diet, obesity, smoking, and physical activity. Certain biological processes, such as inflammation, have also been found to impact the development of atherosclerosis.
Periodontitis, in particular, is an inflammatory condition linked to the development of atherosclerosis-related cardiovascular disease. Periodontal disease is a serious infection of the gums that affects up to 40% of the U.S. population. The disease is caused by bacteria that accumulate on the teeth and gums, typically due to poor dental hygiene.
Although periodontal disease is a well-known risk factor for cardiovascular disease, the exact mechanism connecting the two diseases has been debated for decades. A number of pathomechanisms have been studied with plausible conclusions on why periodontal pathogens are commonly found in atherosclerotic plaques. However, a growing body of scientific evidence points to monocytes as the key to understanding the direct and indirect relationships between periodontal disease and cardiovascular disease.
Introduction and Background Research
Scientists have considered a number of mechanisms for the periodontitis-related development of atherosclerosis, such as involvement of cytokine release induced by dental plaque bacteria and innate immunity activated by bacteremia from dental procedures.
Periodontal disease and atherosclerosis formation may be linked directly via the entry of dental plaque microorganisms into damaged endothelial walls. However, an indirect mechanism may involve the activation of inflammatory molecules induced by the periodontitis condition.
Peripheral blood monocytes of the innate immune system are capable of triggering both periodontal and atherosclerotic diseases. Published data details the presence of phenotypic changes in peripheral blood monocytes in patients with periodontitis, for example, a predominance of T-helper-2 cell responses compared to T-helper-1 responses. Monocytes have been found in an activated state in atherosclerosis and show increased inflammatory response profiles.
Role of Monocytes in Periodontal Disease and Cardiovascular Disease
Multiple in vivo studies have revealed that induced periodontitis leads to the activation of peripheral blood monocytes and upregulation of TNF-alpha and IL-6 proinflammatory genes. This upregulation enhances the adhesion of the monocytes to aortic endothelial walls and triggers atherosclerosis development.
Observations from these studies have established peripheral blood monocytes as an important link between periodontitis and atherosclerotic cardiovascular disease, but the molecular mechanisms underpinning this linkage were unknown until recently.
In 2021, a global team of researchers led by Dr. Wanchen Ning of Southern Medical University in Guangzhou conducted a bioinformatics study analyzing public gene expression profile datasets of peripheral blood monocytes.
The researchers accessed public gene expression data of peripheral blood monocytes that were obtained from patients with periodontitis and from those with atherosclerosis. The analysis uncovered 165 differentially expressed genes that are dysregulated in both periodontitis and atherosclerosis, and a number of the genes may play a role in crosstalk between the two disease states.
Examples of biological processes associated with the identified genes include activation of neutrophils, regulation of leukocyte activation, and vascular endothelial growth factor signaling.
Results of additional expression profile analysis indicate cellular responses to reactive oxygen species and elevated oxygen levels for both disease processes, suggesting that oxidative stress is a shared phenomenon between periodontitis and atherosclerosis.
Overall, the monocyte gene expression analysis results suggest that bacterial invasion of epithelial cells, platelet activation, and the vascular endothelial growth factor signaling pathway represent the most significant processes linking periodontitis and atherosclerosis.
This information may form the basis for further research to determine biomarkers for risk assessment and implementation of preventive measures to lower risk of cardiovascular disease development in patients prone to periodontal disease states.
The data may also be valuable for researchers to identify targets for developing novel therapies for periodontal and cardiovascular diseases.
References Eke PI, Thornton-Evans GO, Wei L, Borgnakke WS, Dye BA, Genco RJ. Periodontitis in US Adults: National Health and Nutrition Examination Survey 2009-2014. J Am Dent Assoc. 2018 Jul;149(7):576-588.e6. doi: 10.1016/j.adaj.2018.04.023. PMID: 29957185; PMCID: PMC8094373.
 Faraedon Z, Sarhang G, Ali A, Aram S, Julian Y. Association Between Periodontal Disease and Atherosclerotic Cardiovascular Diseases: Revisited. Frontiers in Cardiovascular Medicine, Vol. 7. 2021 Jan 15; doi: 10.3389/fcvm.2020.625579.
 Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015 Jan;15(1):30-44. doi: 10.1038/nri3785. PMID: 25534621; PMCID: PMC4276050.
 Fokkema SJ. Peripheral blood monocyte responses in periodontitis. Int J Dent Hyg. 2012 Aug;10(3):229-35. doi: 10.1111/j.1601-5037.2012.00572.x. PMID: 23046009.
 Martínez-García M, Hernández-Lemus E. Periodontal Inflammation and Systemic Diseases: An Overview. Front Physiol. 2021 Oct 27;12:709438. doi: 10.3389/fphys.2021.709438. PMID: 34776994; PMCID: PMC8578868.
 Ning W, Ma Y, Li S, Wang X, Pan H, Wei C, Zhang S, Bai D, Liu X, Deng Y, Acharya A, Pelekos G, Savkovic V, Li H, Gaus S, Haak R, Schmalz G, Ziebolz D, Ma Y, Xu Y. Shared Molecular Mechanisms between Atherosclerosis and Periodontitis by Analyzing the Transcriptomic Alterations of Peripheral Blood Monocytes. Comput Math Methods Med. 2021 Dec 3;2021:1498431.