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Year : 2017  |  Volume : 3  |  Issue : 3  |  Page : 128-132

Periodontal Infection and Cardiovascular Diseases: Vinculum

1 Department of Periodontics, Maulana Azad Institute of Dental Sciences, New Delhi, India
2 Maulana Azad Institute of Dental Sciences, New Delhi, India

Date of Web Publication24-Oct-2017

Correspondence Address:
Titiksha Aggarwal
Maulana Azad Institute of Dental Sciences, Bahadurshah Zafar Marg, New Delhi - 110002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mamcjms.mamcjms_32_17

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In recent years, improved diagnostic tools have broadened the concept of disease therapeutics to encompass and cater all possible etiologies to a particular disease. Cardiovascular diseases are one of the most prevalent disorders in both developing and developed countries. Hence, it is the need of the hour to develop efficient and targeted treatment protocols for them. Holistic management of any disorder is possible only when we are clear with the grass-root level origin and cause of a particular disease. Earlier concepts of pathogenesis of atherosclerosis and cardiovascular events like acute coronary artery syndromes had lipid centric view of etiology. However, in recent years, there has been a shift towards importance of inflammatory processes in the body to be responsible for the disease. Periodontitis is a chronic inflammatory disease with prime bacterial etiology that leads to destruction of supporting structures of teeth. Present is a brief review of the possible mechanisms by which periopathogens can elicit cardiovascular risk and how treatment of periodontal infections can improve systemic health.

Keywords: Atherosclerosis, cardiovascular diseases, oral microbiota, periodontitis

How to cite this article:
Aggarwal T, Lamba AK, Verma M, Aggarwal K, Faraz F, Tandon S. Periodontal Infection and Cardiovascular Diseases: Vinculum. MAMC J Med Sci 2017;3:128-32

How to cite this URL:
Aggarwal T, Lamba AK, Verma M, Aggarwal K, Faraz F, Tandon S. Periodontal Infection and Cardiovascular Diseases: Vinculum. MAMC J Med Sci [serial online] 2017 [cited 2019 Dec 14];3:128-32. Available from: http://www.mamcjms.in/text.asp?2017/3/3/128/217119

  Introduction Top

Atherosclerosis is a slow and progressive chronic inflammatory disease, occurring from a group of specific cellular and molecular responses that leads to lipid and fibrous elements storage in large arteries.[1] Recently, Libby et al.[2] and many others have reported that major component of pathogenesis of cardiovascular disease and, particularly, atheroscelerosis involve multiple components of innate and adaptive immune systems leading to an inflammatory response within the atheromatous lesion. Infection serves as a critical inflammatory stimulus and contributes to both atherogenesis and acute events by coronary plaque destabilization.

Dental plaque is a structured, resilient, yellow-grayish substance adherent tenaciously to intraoral hard structures and is composed of more than 500 distinct microbial species.[3] One individual may harbor 150 or more different species. Mycoplasma, yeast, protozoa, and viruses have also been found apart from bacterial species.[4] Dental plaque is the principal source of infection in the oral cavity, thus serving the stimulus to oral soft tissue inflammation, especially periodontium.

Idiopathic bacteria responsible for periodontal inflammation include Porphyromonas gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans, Prevotella intermedia, Prevotella melaninogenica, Fusobacterium nucleatum, Parvimonas micra, Eikenella corrodens, Prevotella nigrescens, Capnocytophaga gingivalis, Treponema denticola, Treponema socranskii, Eubacterium nodatum, and Campylobacter rectus[5],[6],[7],[8],[9],[10] and many other species like Porphyromonas endodontalis, Prevotella denticola, Filifactor alocis, and other.[11],[12],[13],[14] These bacteria provoke an inflammatory response either by stimulating the release of cytokines and chemoattractants via lipopolysaccharide (LPS) or by directly invading the host tissues. Series of virulence factors are expressed by each distinct species. Majority of bone destruction in periodontitis is brought by host’s immunity by stimulation of matrix metalloproteinase. Induction of athelerosclerotic plaque formation due to raised inflammatory cytokines and chemotactic agents is yet another example of host dysfunction due to heightened immune response. So the question arises whether periodontal infection can induce changes in the distant vascular endothelium.

  Atherogenesis Top

Systemically or locally produced inflammatory cytokines and chemokines assist progression of atherosclerotic plaque formation by upregulation of adhesion molecules (ICAM-1: Intracellular Cell Adhesion Molecule-1, VCAM-1: Vascular Cell Adhesion Molecule-1, E-selectin, and P-selectin) in the vascular endothelium. These changes promote interactions with leukocytes such as monocytes, which promote leukocyte migration into the intimal layer of artery. Lipid streaks comprising modified low density lipoprotein (LDL) and dendritic cells in the intimal layer initiate and propagate this inflammatory response. Endothelial upregulation additionally leads to release of chemotactic cytokines like monocyte chemotactic protein that further attract monocytes and other cells that transport bacteria into the lesion. Dendritic cells and monocytes form foam cells after ingestion of modified LDL. These cells release cytokines, chemoattractants, and matrix metalloproteinases (MMPs). Atherosclerotic plaque maturation entails migration of smooth muscle cells into intima and progressive fibrosis. Mature atheroma is characterized by fibrosis and calcification. This disrupts the blood flow. Injury to the vasculature stimulates thrombin formation which converts fibrinogen to fibrin. Thrombin generation is also associated with plaque rupture. Plaque rupture leads to stroke or myocardial infarction.[15] Inflammatory cytokines and bacterial LPS play a crucial role[16] [Figure 1].
Figure 1: Diagrammatic representation of atherogenesis

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  Mechanisms Linking Periodontitis with Cardiovascular Risk Top

Several studies showed an association between periodontitis and endothelial dysfunction, highlighting a possible causal relationship between atherosclerosis and periodontitis.[17],[18] Several proposed mechanisms associating periodontitis with CVD have been described.

Increased systemic mediators of inflammation

Numerous studies have shown increased systemic mediators of inflammation in periodontitis patients as shown in [Table 1].[16]
Table 1: Inflammatory mediators and association with cardiovascular disease (CVD)

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It has been hypothesized that these inflammatory cytokines and chemotactic mediators released in periodontal lesions could “spill over” into the circulation. If it occurs then they may achieve sufficient concentrations with preserved bioactivity to impact distant tissues and organs.

Bacterial invasion of host cells

Invasion of bacteria into the host cells is a key virulent property which provides a privileged niche to it by providing access to host protein, iron, and other nutritional substrates, a shelter from certain immune responses, and a mechanism for persistence in the infected tissue. Intracellular habitat also protects these bacteria from antimicrobial agents.[19] Meyer et al.[20] provided first evidence that A. actinomycetemcomitans invaded KB carcinoma (keratin forming tumor lines). [Table 2] is showing the periopathogens with their virulent properties which show tissue invasion associated with cardiovascular risk.
Table 2: Data compiled from article by European Federation of Periodontology and American Academy of Periodontology 2013[21]

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Molecular mimicry

Periodontitis is associated with elevated systemic antibody responses to a variety of periodontal pathogens, and many of these microbes are known to be able to induce cross-reactive and specific antibodies of relevance to atherosclerosis risk.
  1. Heat shock proteins (HSPs) are antigens expressed by certain microbes and also by certain host cells, for example, human HSP60 is expressed by endothelial cells. Periodontal pathogens, including P. gingivalis, also express HSPs such as HSP60 (GroEL).[22] Antibody response elicited toward bacterial HSP can produce cross reactivity with the host endothelial HSPs, thus promoting atheroma formation. Elevated serum levels of anti-F. nucleatum GroEl has also been seen.[23] Anti-T. forsythia, anti-A. actinomycetemcomitans, and anti-P. gingivalis HSPs are cross-reactive with each other and with human HSP.[24] P. gingivalis HSP60 contains both B- and T-cell epitopes cross-reactive with hHSP60.[25]
  2. Anticardiolipin antibodies have also been found associated with vascular thrombosis and early atherosclerosis. Many microbes induce anticardiolipin antibody formation due to their similarities to peptide sequence in β2GP1. One such sequence in β2GP1 is TLRVYK (hexapeptide). Peptide sequence SIRVYK is homologous to TLRVYK. This peptide sequence was found in A. actinomycetemcomitans.[26] Thus, it was proposed that A. actinomycetemcomitans produces antibodies which induce atherosclerosis.

Serum LDL and high density lipoprotein (HDL)

Presence of LPS in plasma and acute phase responses to systemic dissemination of bacteria promotes biosynthesis of cholesterol in the liver which is transported as serum lipids capable of binding to bacterial LPS. Losche et al.[27] reported that chronic periodontitis (CP) patients exhibited higher levels of total cholesterol and serum LDL than control subjects. This observation has been repeated in other studies. Katz et al.[28] and Nibali et al.[29] observed elevation in serum LDL levels as well as decreases in HDL levels in periodontitis patients who were otherwise healthy, along with significantly elevated white cell counts. These relationships were seen in nonsmokers as well as in smokers. Studies evaluating the density of LDL in periodontitis patients have also found higher levels of atherogenic small dense LDL in CP patients[30] and in aggressive periodontitis patients.[31]

Common genetic risk factors

Various genome-wide association studies[32],[33],[34],[35] on susceptibility locus for CVD have concluded ANRIL locus (a long intergenic non coding RNA within Chr9p21) to be best replicated in coronary heart disease associated risk patients. Schaefer et al.[36],[37] and Ernst et al.[38] have found highly significant risk of aggressive periodontitis with variants of ANRIL. However, very limited evidence exists in support of ANRIL in CP patients till date. Moreover, frequency of some ANRIL variants in Dutch CP patients was significantly higher than German showing some ethnic variation.

The effect of periodontal treatment on endothelial function has also been evaluated, showing that its treatment reverses endothelial dysfunction frame associated with periodontitis.[17],[18],[39],[40]

  Conclusion Top

The occurrence of atherosclerosis cannot be fully explained by classical risk factors.[28] Missing links between periodontal infection and cardiovascular disease are still being explored. However, evidences till date direct towards treating periodontal disease as an essential part of prevention and management of cardiovascular diseases.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1]

  [Table 1], [Table 2]


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