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Update on the Oral-Systemic Link

As science’s understanding of the role of inflammation evolves, the oral-systemic association between periodontal disease and a broad array of other inflammatory conditions becomes clearer.

This course was published in the January 2020 issue and expires January 2023. The author has no commercial conflicts of interest to disclose. This 2 credit hour self-study activity is electronically mediated.


After reading this course, the participant should be able to:

  1. Explain the current understanding of inflammation’s role in the association between oral and systemic diseases.
  2. Discuss the prevalence of periodontitis and the processes involved in this disease, as well as the association between periodontal inflammation and systemic conditions, such as cardiovascular disease and diabetes.
  3. Describe some of the ways in which inflammation can be mediated or resolved.

This review will focus on our new understanding of the role of inflammation in the periodontal disease/systemic disease connection. While there is an emerging literature for relationships between periodontitis and a broad array of inflammatory diseases, the majority of the data involve the study of Type 2 diabetes (T2D) and cardiovascular diseases (CVD). Thus, these two diseases and their relationship to each other and periodontitis will be discussed, with an emphasis on the inflammatory processes that link them together.

The etiology for the inflammatory disease periodontitis is bacterial plaque, now referred to as the periodontal microbiome, but the pathogenesis of the disease — and the mechanisms of tissue breakdown and progressive bone loss — are immune-inflammatory. In the oral cavity, the tooth crown is colonized by commensal bacteria in organized bacterial biofilms, commonly known as plaque. Periodontal disease begins with gingivitis, which is an inflammation of the gingiva induced by chronic exposure to dental biofilm. Gingivitis progresses from the initial neutrophil-dominated lesion to a mature immune lesion dominated by B and plasma cells. In the advanced lesion, there is loss of gingival collagen, which is reversible by removing the plaque.1 Periodontitis is characterized by irreversible loss of attachment, with concomitant alveolar bone loss. The composition of the periodontal microbiome in periodontitis is more complex; it is more dominated by gram negative bacteria, and the bacterial load significantly increases. It is characterized as a chronic inflammatory lesion, with loss of tissue homeostasis. It remains unknown why gingivitis is stable in some people and progresses to periodontitis in others.

The temporal sequence of change to the oral microbiome and development of periodontitis is important. Earlier dogma blamed specific pathogens as the cause of disease; this is no longer considered valid, since we now know the bacteria associated with disease are commensals, including the pathogens. Overgrowth of minor components of the biofilm creates a dysbiotic microbiome. The reason for the shift is inflammation that changes the bacterial growth environment. This concept was first proposed by Marsh.2 The subgingival environment is a natural selection pressure that impacts the specific microbial composition. Plaque accumulation leads to inflammation within the gingival tissues and, ultimately, gingivitis. Inflammation dictates the environmental changes within the gingival sulcus favoring the growth of proteolytic species of bacteria.

This inflammatory response further enriches the environment via tissue-breakdown products that enhance the growth of pathogens. The American Academy of Periodontology has changed its definition for the etiology and pathogenesis of periodontitis from infectious to inflammatory. This also changes the treatment target from control of the commensal flora to controlling inflammation.3,4 Bacteria are the principal cause of gingivitis, but the host response determines whether the disease progresses.5,6 Overwhelming evidence now demonstrates that uncontrolled inflammation amplified by immune responses is largely responsible the tissue destruction in periodontitis.7,8


To understand the role of inflammation in the relationship between periodontitis and systemic diseases, it is necessary to understand how inflammation is naturally regulated. This is an important topic because our knowledge of this process has exploded in the last decade or so. With periodontitis, the pro-inflammatory mediators — cytokines, chemokines and metalloproteinases — increase dramatically in periodontal tissues and gingival crevicular fluid.9–11 The early response lipid mediators, leukotriene B4 and prostaglandin E2, are especially increased.12 The pathophysiology of periodontitis is attributable to the actions of these lipid mediators.13–15 Cyclooxygenases (COX), the enzymes that make prostaglandins (particularly COX-2), are increased in periodontal tissue in disease.16–20 These same mediators play an important role in the pathogenesis of T2D, as will be discussed below.

The termination sequence of inflammation is now known to be an active process driven by a distinct set of lipid mediators that resolve inflammation. These are the products of enzymes called lipoxygenases (LOX), and their products include molecules called lipoxins from arachidonic acid, and resolvins, protectins and maresins from Omega-3 fatty acids. The description of these complex pathways is beyond the scope of this review, and the reader is directed to comprehensive reviews of this biology for further information.21,22 What is important to understand is that resolution of inflammation is an active process — not a passive decay of proinflammatory molecules, as previously believed. These inflammatory-resolving mediators bind to specific receptors on inflammatory cells, so it is a feed-forward system in which termination of inflammation is actively directed, not inhibited. Inhibition of inflammation is fraught with side effects, however, such as increased susceptibility to infection. This does not occur with natural resolution of inflammation.21

The role of these molecules in periodontitis is exemplified in studies of localized aggressive periodontitis (LAP), a rapidly progressing form of the disease. Investigations of inflammatory-resolving mediators in LAP revealed aberrant LOX activity in whole blood of LAP patients23 that was associated with significantly greater platelet-neutrophil and platelet-monocytes aggregates. Defective macrophage phagocytosis in LAP was also seen. Simply stated, LAP was characterized by a failure to resolve inflammation, which led to the progression of periodontal disease. Fredman et al23 also reported the LAP abnormalities were reversed with addition of mediators of resolution. Other investigations of proresolution mediators by Hasturk et al24 showed that LAP neutrophils do not respond well to mediators of resolution.

Excessive inflammation is a critical component of the most common diseases of aging, including periodontitis, T2D and CVD. The reasons for excess inflammation are not fully understood, but there are associations with obesity and other risk factors. Importantly, there is also a potentially critical role for the microbiome that is just beginning to be explored. Diabetes mellitus, particularly Type 2, is characterized by complications that increase with poor glycemic control. These include periodontitis and CVD. Approximately 50% of the U.S. population has some degree of periodontal disease. Having T2D doubles that risk.25 In addition, T2D increases the risk for CVD four times (Framingham Heart Study) and accounts for most premature deaths in patients with T2D.26 Inflammation is a major link between T2D and its complications.26,27 In periodontitis, the shift to chronicity and persistence of pathogens (dysbiosis) results from increased inflam­mation,28–32 leading to leukocyte-mediated tissue destruction. Patients with T2D who display increased inflammation are refractory to standard periodontal therapy, which further emphasizes the interrelationship between inflammation and the pathogenesis of these two diseases.33,34


How obesity, T2D and its complications of periodontitis and CVD are linked at a cell biology mechanistic level is unclear. Neutrophil and macrophage interactions with platelets are poorly regulated in individuals with periodontitis or T2D.35,36 These “smoking gun” associations suggest that mechanisms related to inflammation in periodontitis may be linked with the primary cause of mortality in patients with diabetes — CVD. It is also well established that sufficient proresolution agonist concentrations are necessary to prevent tissue damage in inflammation,24,31 and these pathways are deficient in obesity and T2D.37

Periodontitis, T2D and CVD all involve inflammation-mediated microvascular and macrovascular changes, disruption of lipid metabolism, glycosylation of proteins, and other abnormalities that result from dysregulation of inflammation. In periodontitis and T2D, uncontrolled inflammation causes dysbiosis in the mouth and gut. Dysbiosis in the gut results in changes in gut permeability that increases systemic inflammation and insulin resistance. Dysregulation of inflammation is central to T2D and its periodontal complications. Active resolution of inflammation appears to be compromised in obesity and T2D.38 Omega 3 fatty acids and an increased omega-3/omega-6 ratio are found in populations with lower prevalence of coronary artery disease.39 Omega-3 active metabolites, particularly resolvins, are able to reduce obesity-associated inflammation and insulin resistance.40,41

Emerging evidence suggests that non-resolving inflammation is a critical underlying factor of both periodontitis and T2D.23,42–44 To further investigate the comorbidity of periodontitis and T2D, studies were performed using a human resolvin E1 receptor (RvE1 receptor)-overexpressing diabetic transgenic mouse. Resolvin E1 (RvE1) is one of the resolvins derived from eicosapentaenoic acid. Studies in genetically modified mice are a powerful tool for assessing the role of specific molecules in health and disease. Knocking out a gene or overexpressing a gene may provide loss-of-function and gain-of-function data, respectively. Genes code for proteins and, in this case, the resolvins, are lipids. For this reason, the receptor for the lipid was overexpressed to see what gain-of-function of the resolvin did to the disease.

Several important observations were made in these studies. The ERV1 transgenic mouse proved to be an excellent gain-of-function model for demonstrating the actions of resolvins.45 The phenotype of the ERV1 transgenic exhibited a reduced inflammatory response, with an increased response to RvE1. The ERV1 transgenic mouse is resistant to periodontitis. Diabetic mice experience significantly more periodontitis than wild type, and ERV1 transgenic mice with T2D are protected from periodontitis — and the addition of topical RvE1 makes them even more resistant. Diabetic mice have impaired neutrophil phagocytosis of the periodontal pathogen Porphyromonas gingivalis, and clearance of the same pathogen was deficient, so more severe tissue damage was evident.46 Adding RvE1 to the phagocytosis assay increased P. gingivalis phagocytosis and killing by neutrophils by the transgenic diabetic animals. Adding RvE1 also decreased the influx of inflammatory cells and improved P. gingivalis clearance. This is an important observation because it suggests that excess inflammation makes infections worse, not better. Looking at the subcellular level, incubation of neutrophils with P. gingivalis-induced proinflammatory signaling though phosphorylation of the intracellular enzymes Akt and MAPKinase was dampened by RvE1. Altogether, the data show that RvE1 increases phagocytosis and reduces collateral tissue damage.

The direct action of RvE1 on the development of diabetes was also noted. For example, ERV1 transgenic diabetic mice had significantly reduced fat accumulation. At the same time, inflammatory macrophage accumulation in the fat was significantly reduced, with reduced production of inflammatory mediators by fat tissue. Less inflamed fat tissue is likely contributing to the non-inflammatory phenotype and protection from disease.47 These observations were further supported by the work of Sima et al,48 who showed that ERV1 transgenic mice did not gain as much weight and were protected from the onset on T2D.

Increased inflammation in T2D directly contributes to increased prevalence and severity of periodontitis in individuals with T2D.49 Diabetes and periodontal disease are reciprocal. Periodontal infections significantly impact diabetic control, and diabetes is a significant risk factor for periodontal disease.50 A substantial increase in obesity (which is the main risk factor for T2D), and the high rates of impaired glucose tolerance found in the third National Health and Nutrition Examination Survey (NHANES III), suggest that diabetes will grow as a major health problem in the U.S.51 Non-resolving inflammation is a critical factor in periodontitis and T2D that is associated with a deficiency in mediators of resolution of inflammation.


The ischemic complications of CVD include myocardial infarction and stroke, which are leading causes of morbidity and mortality in the U.S.52 In fact, 70% of the aging population experiences CVD.53 The underlying cause is atherosclerosis that progresses for years without symptoms. Catastrophic acute ischemic events (thrombosis) occur when an atheromatous plaque disrupts.54,55 Inflammation is a central determinant in the pathogenesis of plaque formation and rupture;56,57 in fact, uncontrolled systemic inflammation is a predictor of CVD events. Local inflammatory foci, such as chronic periodontitis, induce systemic inflammation.58–60 Periodontal disease risk factors are shared characteristics with CVD. These include being older, and exhibiting similar stress and smoking behaviors; male gender also increases risk.61 Periodontal disease and CVD co-segregate in the population.62,63 In addition, in the joint European Federation of Periodontology/American Academy of Periodontology Workshop on Periodontitis and Systemic Diseases published in 2013, the consensus of thought leaders in the U.S. and Europe was that periodontitis clearly imparts excess risk for T2D and CVD,64,65 and enhances CVD in animal models.66,67

Prospective studies in animals have been used to demonstrate that periodontitis increases large vessel atherogenesis. In the high-fat-diet rabbit model,67,68 the New Zealand white rabbit serves as a model for periodontitis with similar characteristics to humans. High-fat-diet-induced atherogenesis is induced simultaneously, and inflammatory changes can be tracked locally and in the vessel wall. This model was used to demonstrate the impact on atherogenesis with periodontal treatment using resolution of inflammation mediators.68 The investigators showed that oral-topical treatment to the gingiva provided dose-dependent protection against the onset of periodontitis and atherogenesis. In addition, they noted a reduced intima/media ratio in the walls of major vessels (which is a cardinal sign of CVD). A decreased inflammatory cell infiltrate was also seen, demonstrating the impact of local inflammatory foci on the initiation of CVD. These data suggest that mediators of resolution of inflammation are rapidly absorbed through the mucosa to provide systemic actions that are extremely potent, exhibiting marked reductions in systemic inflammation and blocking atherogenesis at extremely low doses.

In atherogenesis, macrophage activation and the phenotype of the macrophage (proinflammatory or pro-resolution) — called class switching — are critical for foam cell formation.69 Macrophage activation occurs, at least in part, through a surface receptor molecule called cluster of differentiation (CD) 36, which is a scavenging receptor critical for internalization of oxidized low density lipoprotein (oxo-LDL).70 CD36 is activated by a high-cholesterol diet and causes macrophage mediated foam cell formation. P. gingivalis stimulates CD36 and oxo-LDL activation, leading to the activation of pathways that generate proinflammatory molecules.71 CD36/oxo-LDL activity and macrophage foam cell formation increase the proinflammatory cytokines interleukin (IL)-8, IL-6, IL-18, tumor necrosis factor-α, monocyte chemotactic protein-1, and matrix metalloproteinase (MMP)-2 and MMP-9; they also decrease the anti-inflammatory cytokine, IL-10.72,73 P. gingivalis-mediated stimulation of this mechanism can be mediated through toll-like receptor (TLR)2 and TLR4 recognition, and TLR2 binding to lipopolysaccharide results in pro-atherogenic events.74 Docosahexaenoic acid, which is an omega-3 fatty acid precursor of D-class resolvins, has been found to decrease IL-6 and IL-8 production through CD36-mediated activity.75


A greater understanding of regulation pathways of inflammation has deepened our understanding of the etiology and pathogenesis of periodontal disease. It is now understood that periodontitis is an inflammatory disease initiated by commensal bacteria. Current evidence points to inflammation driving changes in the commensal microbiome that amplify the inflammatory response.

The discovery there are pathways of active resolution of inflammation has provided new targets for natural control of inflammation. When it comes to periodontitis and related systemic diseases, the evidence points to a failure of resolution pathways. However, the level at which the failure occurs is unknown, so there is much work to be done. Understanding how this works in each patient exemplifies the goals of precision medicine.

As our knowledge of the actions of pro-resolution mediators evolves, the potential for the production of new drugs for the control of inflammatory diseases increases.

Acknowledgements: U.S. Public Health Service Grants DE025020 and 025383 from the National Institutes of Dental and Craniofacial Research supported part of this research.


  1. Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. a summary of current work. Lab Invest. 1976;34:235–249.
  2. Marsh PD. Microbial ecology of dental plaque and its significance in health and disease. Adv Dent Res. 1992;8:263–271.
  3. Van Dyke TE. Inflammation and periodontal diseases: a reappraisal. J Periodontol. 2008;79(8 Suppl):1501–1502.
  4. Van Dyke TE. The management of inflammation in periodontal disease. J Periodontol. 2008;79(8 Suppl):1601–1608.
  5. Kornman KS, Page RC, Tonetti MS. The host response to the microbial challenge in periodontitis: Assembling the players. Periodontology 2000. 1997;14:33–53.
  6. Page RC, Kornman KS. The pathogenesis of human periodontitis: an introduction. Periodontol 2000. 1997;14:9–11.
  7. Page RC, Offenbacher S, Schroeder HE, Seymour GJ, Kornman KS. Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions. Periodontol 2000. 1997;14:216–248.
  8. Vandenberg JI, Conigrave A, King GF, Kirk K. 2013. From kinetics to imaging: an nmr odyssey–a festschrift symposium in honour of Philip William Kuchel. Eur Biophys J. EBJ. 2013;42:1–2.
  9. Assuma R, Oates T, Cochran D, Amar S, Graves DT. IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. J Immunol. 1998;160:403–409.
  10. Gainet J, Chollet-Martin S, Brion M, Hakim J, Gougerot-Pocidalo MA, Elbim C. Interleukin-8 production by polymorphonuclear neutrophils in patients with rapidly progressive periodontitis: an amplifying loop of polymorphonuclear neutrophil activation. Lab Invest. 1998;78:755–762.
  11. Romanelli R, Mancini S, Laschinger C, Overall CM, Sodek J, McCulloch CA. Activation of neutrophil collagenase in periodontitis. Infection and immunity. 1999;67:2319–2326.
  12. Offenbacher S, Odle BM, Van Dyke TE. The use of crevicular fluid prostaglandin E2 levels as a predictor of periodontal attachment loss. J Periodont Res. 1986;21:101–112.
  13. Klein DC, Raisz LG. Prostaglandins: stimulation of bone resorption in tissue culture. Endocrinology. 1970;86:1436-1440.
  14. Raisz LG, Koolemans-Beynen AR. Inhibition of bone collagen synthesis by prostaglandin E2 in organ culture. Prostaglandins. 1974;8:377–385.
  15. Solomon LM, Juhlin L, Kirschenbaum MB. 1968. Prostaglandin on cutaneous vasculature. J Investig Dermatol. 1968;51:280–282.
  16. Albers HK, Loning T, Lisboa BP. Biochemical and morphologic studies on prostaglandins E and F in the normal and inflamed gingiva. Deutsche zahnarztliche Zeitschrift. 1979;34:440–443.
  17. ElAttar TM. Prostaglandin E2 in human gingiva in health and disease and its stimulation by female sex steroids. Prostaglandins. 1976;11:331–341.
  18. ElAttar TM, Lin HS, Tira DE. The relationship between the concentration of female sex steroids and prostaglandins production by human gingiva in vitro. Prostaglandins Leukot Med. 1982;8:447–458.
  19. ElAttar TM, Lin HS, Tira DE. 1984. Arachidonic acid metabolism in inflamed gingiva and its inhibition by anti-inflammatory drugs. J Periodontol. 1984;55:536–539.
  20. Pouliot M, Clish CB, Petasis NA, Van Dyke T, Serhan CN. Lipoxin A(4) analogues inhibit leukocyte recruitment to Porphyromonas gingivalis: a role for cyclooxygenase-2 and lipoxins in periodontal disease. Biochemistry. 2000;39:4761–4768.
  21. Serhan CN. Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms. FASEB J. 2017;31:1273–1288.
  22. Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nature Rev Immunol. 2008;8:349–361.
  23. Fredman G, Oh SF, Ayilavarapu S, Hasturk H, Serhan CN, Van Dyke TE. Impaired phagocytosis in localized aggressive periodontitis: rescue by resolvin E1. PloS One. 2001;6:e24422.
  24. Hasturk H, Kantarci A, Ohira T, et al. Rve1 protects from local inflammation and osteoclast–mediated bone destruction in periodontitis. FASEB J. 2006;20:401–403.
  25. Eke PI, Dye BA, Wei L, et al.  Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res. 2012;91:914–920.
  26. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868–874.
  27. Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation. 2005;111:1448–1454.
  28. Andoh A, Tsujikawa T, Sasaki M, et al. Faecal microbiota profile of Crohn’s disease determined by terminal restriction fragment length polymorphism analysis. Aliment Pharmacol Ther. 2009;29:75–82.
  29. Braun J, Wei B. Body traffic: ecology, genetics, and immunity in inflammatory bowel disease. Annu Rev Pathol. 2007;2:401–429.
  30. Champion OL, Valdez Y, Thorson L, et al. A murine intraperitoneal infection model reveals that host resistance to campylobacter jejuni is Nramp1 dependent. Microbes Infect. 2008;10:922–927.
  31. Hasturk H, Kantarci A, Goguet-Surmenian E, et al. Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol. 2007;179:7021–7029.
  32. Shih DQ, Targan SR, McGovern D. Recent advances in IBD pathogenesis: genetics and immunobiology. Curr Gastroenterol Rep. 2008;10:568–575.
  33. Borgnakke W, Chapple I, Genco R, et al. The randomized controlled trial (RCT) published by the Journal of the American Medical Association (JAMA) on the impact of periodontal therapy on glycated hemoglobin (HbA1c) has fundamental problems. J Evid Base Dent Pract. 2014;14:127–132.
  34. Engebretson SP, Hyman LG, Michalowicz BS, et al. The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons with type 2 diabetes and chronic periodontitis: a randomized clinical trial. JAMA. 2013;310:2523–2532.
  35. Fredman G, Van Dyke T, Serhan C. Resolvin E1 regulates adenosine diphosphate activation of human platelets. Arterioscler Thromb Vas Biol. 2010;30:2005–2013.
  36. Tuttle HA, Davis-Gorman G, Goldman S, Copeland J, McDonagh P. Platelet-neutrophil conjugate formation is increased in diabetic women with cardiovascular disease. Cardiovasc Diabetol. 2003;2:12.
  37. Khanna S, Biswas S, Shang Y, et al. Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PloS One. 2010;5:e9539.
  38. Freire MO, Dalli J, Serhan CN, Van Dyke TE. Neutrophil resolvin E1 receptor expression and function in type 2 diabetes. J Immunol. 2017;198:718–728.
  39. Bang HO, Dyerberg J, Sinclair HM. The composition of the Eskimo food in north western greenland. Am J Clin Nutr. 1980;33:2657–2661.
  40. Claria J, Dalli J, Yacoubian S, Gao F, Serhan CN. Resolvin D1 and resolvin D2 govern local inflammatory tone in obese fat. J Immunol. 2012;189:2597–2605.
  41.  Gonzalez-Periz A, Horrillo R, Ferre N, et al. Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J. 2009;23:1946–1957.
  42. Merched AJ, Ko K, Gotlinger KH, Serhan CN, Chan L. Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB J. 2008;22:3595–3606.
  43. Nathan C, Ding A. Nonresolving inflammation. Cell. 2010;140:871–882.
  44. Oh SF, Dona M, Fredman G, Krishnamoorthy S, Irimia D, Serhan CN. Resolvin E2 formation and impact in inflammation resolution. J Immunol. 2012;188:4527–4534.
  45. Gao L, Faibish D, Fredman G, et al. Resolvin E1 and chemokine-like receptor 1 mediate bone preservation. J Immunol. 2013;190:689–694.
  46. Sin YM, Sedgwick AD, Chea EP, Willoughby DA. Mast cells in newly formed lining tissue during acute inflammation: a six day air pouch model in the mouse. Ann Rheum Dis. 1986;45:873–877.
  47. Herrera BS, Hasturk H, Kantarci A, et al. Impact of resolvin E1 on murine neutrophil phagocytosis in type 2 diabetes. Infec Immun. 2015;83:792–801.
  48. Sima C, Montero E, Nguyen D, et al. ERV1 overexpression in myeloid cells protects against high fat diet induced obesity and glucose intolerance. Sci Rep. 2017;7:12848.
  49. Iacopino AM. Periodontitis and diabetes interrelationships: role of inflammation. Ann Periodontol. 2001;6:125–137.
  50. Löe H. Periodontal disease. The sixth complication of diabetes mellitus. Diabetes Care. 1993;16:329–334.
  51. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414:782–787.
  52. Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics—2009 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119:480-486.
  53. Papadopoulos G, Shaik-Dasthagirisaheb YB, Huang N, et al. Immunologic environment influences macrophage response to Porphyromonas gingivalis. Mol Oral Microbiol. 2017;32:250–261.
  54. Feltes TF, Bacha E, Beekman RH 3rd, et al. Indications for cardiac catheterization and intervention in pediatric cardiac disease: a scientific statement from the American Heart Association. Circulation. 2011;123:2607–2652.
  55. Verbrugghe E, Boyen F, Gaastra W, et al. The complex interplay between stress and bacterial infections in animals. Vet Microbiol. 2012;155:115–127.
  56. Campbell LA, Rosenfeld ME. Infection and atherosclerosis development. Arch Med Res. 2015;46:339–350.
  57. Lindy O, Suomalainen K, Mäkelä M, Lindy S. Statin use is associated with fewer periodontal lesions: a retrospective study. BMC Oral Health. 2008;8:16.
  58. Chung HY, Lee EK, Choi YJ, et al. Molecular inflammation as an underlying mechanism of the aging process and age-related diseases. J Dent Res. 2011;90:830–840.
  59. Kantarci A, Yen S, Will LA. Conclusion and future directions. Front Oral Biol. 2016;18:130.
  60. Subramanian S, Emami H, Vucic E, et al. High-dose atorvastatin reduces periodontal inflammation: A novel pleiotropic effect of statins. J Am Coll Cardiol. 2013;62:2382–2391.
  61. Bertoni A, Rastoldo A, Sarasso C, et al. Dehydroepiandrosterone-sulfate inhibits thrombin-induced platelet aggregation. Steroids. 2012;77:260–268.
  62. Berr SS, Brookeman JR. On MR imaging of atheromatous lipids in human arteries. J Magn Reson Imaging. 1995;5:373–374.
  63. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACFF/​AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/​American Heart Association Task Force on practice guidelines. Circulation. 2011;124:2761–2796.
  64. Chapple IL, Genco R, Working Group 2 of the Joint EFP/​AAP Workshop. Diabetes and periodontal diseases: consensus report of the joint EFP/​AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontal. 2013;40(Suppl 14):S106–S112.
  65. Dietrich T, Sharma P, Walter C, Weston P, Beck J. The epidemiological evidence behind the association between periodontitis and incident atherosclerotic cardiovascular disease. J Clin Periodontal. 2013;40(Suppl 14):S70–S84.
  66. Giugliano RP, Braunwald E. The year in non-st-segment elevation acute coronary syndrome. J Am Coll Cardiol. 209;54:1544–1555.
  67. Jain A, Batista EL Jr, Serhan C, Stahl GL, Van Dyke TE. Role for periodontitis in the progression of lipid deposition in an animal model. Infec Immun. 2003;71:6012–6018.
  68. Hasturk H, Abdallah R, Kantarci A, et al. Resolvin E1 (RvE1) attenuates atherosclerotic plaque formation in diet and inflammation-induced atherogenesis. Arterioscler Thromb Vasc Biol. 2015;35:1123–1133.
  69. Di Pietro N, Formoso G, Pandolfi A. Physiology and pathophysiology of oxLDL uptake by vascular wall cells in atherosclerosis. Vascul Pharmacol. 2016;84:1–7.
  70. Jay AG, Chen AN, Paz MA, Hung JP, Hamilton JA. CD36 binds oxidized low density lipoprotein (LDL) in a mechanism dependent upon fatty acid binding. J Biol Chem. 2015;290:4590–4603.
  71. Brown PM, Kennedy DJ, Morton RE, Febbraio M. CD36/​SR-b2-TLR2 dependent pathways enhance porphyromonas gingivalis mediated atherosclerosis in the Ldlr KO mouse model. PloS One. 2015;10:e0125126.
  72. Bekkering S, Quintin J, Joosten LA, van der Meer JW, Netea MG, Riksen NP. Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes. Arterioscler Thromb Vasc Biol. 2014;34:1731–1738.
  73. Bzowska M, Nogiec A, Skrzeczynska-Moncznik J, Mickowska B, Guzik K, Pryjma J. Oxidized LDLs inhibit TLR-induced IL-10 production by monocytes: A new aspect of pathogen-accelerated atherosclerosis. Inflammation. 2012;35:1567–1584.
  74. Chávez-Sánchez L, Garza-Reyes MG, Espinosa-Luna JE, Chavez-Rueda K, Legorreta-Haquet MV, Blanco-Favela F. The role of TLR2, TLR4 and CD36 in macrophage activation and foam cell formation in response to oxLDL in humans. Human Immunol. 2014;75:322–329.
  75. Shikama Y, Kudo Y, Ishimaru N, Funaki M. Possible involvement of palmitate in pathogenesis of periodontitis. J Cell Physiol. 2015;230:2981–2989.

From Decisions in Dentistry. January 2020;6(1):25–29.

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