Abstract
Introduction
To investigate the potential link between apical periodontitis (AP) and cardiovascular
(CV) function, inflammation markers, endothelial flow reserve (EFR), and levels of
asymmetrical dimethylarginine (ADMA), the endogenous inhibitor of nitric oxide synthase
(NOS), were measured in young adults with AP aged 20–40 years of both sexes.
Methods
Forty men and 41 women (31 ± 5.71 years) free from periodontal disease, CV disease,
and traditional CV risk factors were enrolled in the study. Twenty men and 21 women
had AP; 40 healthy individuals matched for age, sex, and physical characteristics
were also recruited as controls. All subjects underwent dental and complete physical
examination, electrocardiography, conventional and tissue Doppler imaging echocardiography,
and measurement of EFR. Interleukin (IL)-2, tumor necrosis factor alpha, reactive
oxygen species (ROS), and ADMA were also assessed. Data were analyzed using the 2-tailed
Student t test, the Pearson t test (or the Spearman t test for nonparametric variables), and multivariate linear regression analysis.
Results
Echocardiography excluded any morphologic and functional cardiac alteration in all
the subjects studied. Patients with AP of both sexes showed a significant reduction
in EFR (P < .05) and a significant increase in IL-2 (men: P < .01, women: P < .05), whereas ROS were increased significantly only in women (P < .05). ADMA levels were unchanged in women with AP, but they were significantly
increased in men (P < .05). A significant direct correlation between ADMA and IL-2 (r = 0.67, P < .001) and an inverse correlation between ADMA and EFR (r = −0.42, P < .05) in men and a significant inverse correlation between ROS and EFR (r = −0.71, P < .01) in female patients were observed.
Conclusions
The presence of chronic inflammation in young adults with AP may cause early endothelial
dysfunction documented by the reduced EFR. AP in men may influence the metabolism
of NOS, whereas in women it appears to implicate a more direct detrimental mechanism.
This difference is sex dependent and may be attributable to the protective action
of estrogen in women.
Key Words
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References
- Atherosclerosis—an inflammatory disease.N Engl J Med. 1999; 340: 115-126
- Classification, diagnosis and clinical manifestations of apical periodontitis.Endod Topics. 2004; 8: 36-54
- Periapical lesions of endodontic origin.in: Ingle J.I. Bakland L.K. Baumgartner J.C. Ingle's Endodontics. 6th ed. Hamilton, Ontario, Canada: BC Decker, 2008: 494-519
- Overlapping protective and destructive regulatory pathways in apical periodontitis.J Endod. 2014; 40: 155-163
- Association of endodontic infection with detection of an initial lesion to the cardiovascular system.J Endod. 2011; 37: 1624-1629
- Three decades of endothelium research: from the detection of nitric oxide to the everyday implementation of endothelial function measurements in cardiovascular diseases.Swiss Med Wkly. 2010; 140: w13122https://doi.org/10.4414/smw.2010.13122
- Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events.Eur Heart J. 2010; 31: 1142-1148
- Markers of inflammation and risk of coronary heart disease.Dis Markers. 2009; 26: 217-225
- Novel mechanism for endothelial dysfunction dysregulation of dimethylarginine dimethylaminohydrolase.Circulation. 1999; 99: 3092-3095
- Does ADMA cause endothelial dysfunction?.Arterioscler Thromb Vasc Biol. 2000; 20: 2032-2037
- Reduction of NO- and EDHF-mediated vasodilatation in hypertension: role of asymmetric dimethylarginine.Clin Exp Hypertens. 2007; 29: 489-501
- Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure.Eur Heart J. 2008; 29: 2506-2513
- Impact of asymmetric dimethylarginine on mortality after acute myocardial infarction.Arterioscler Thromb Vasc Biol. 2008; 28: 954-960
- Nitric oxide and oxidative stress in vascular disease.Pflugers Arch. 2010; 459: 923-939
- Assessment of regional systolic and diastolic wall motion velocities in highly trained athletes by pulsed wave Doppler tissue imaging.J Am Soc Echocardiogr. 2002; 15: 900-905
- Lesions of endodontic origin and risk of coronary heart disease.J Dent Res. 2006; 85: 996-1000
- Association between chronic apical periodontitis and coronary disease.J Endod. 2014; 40: 164-167
- The relationship between self-reported history of endodontic therapy and coronary heart disease in the Atherosclerosis Risk in Communities Study.J Am Dent Assoc. 2009; 140: 1004-1012
- Pulpal inflammation and incidence of coronary heart disease.J Endod. 2006; 32: 99-103
- Relationship between smoking and endodontic variables in Hypertensive patients.J Endod. 2011; 37: 764-767
- Endodontic variables and coronary heart disease.Acta Odontol Scand. 2003; 61: 257
Frisk F. Epidemiological aspects on apical periodontitis. Studies based on the prospective population study of women in Göteborg and the population study on oral health in Jönköping, Sweden [thesis]. Göteborg, Sweden: Department of Endodontology/Oral Diagnosis Institute of Odontology, The Sahlgrenska Academy, Göteborg University; 2007.
- Hypertension and dental periapical condition.J Endod. 2010; 36: 1800-1804
- Atherosclerosis-associated endothelial dysfunction.Z Kardiol. 2000; 89: 70-74
- Markers of endothelial dysfunction.Clin Chem Lab Med. 2000; 38: 77-85
- Interleukin-2 in the development and control of inflammatory disease.Immunol Rev. 2008; 226: 19-28
- The regulatory, inflammatory, and T cell programming roles of interleukin-2 (IL-2).J Autoimmun. 2008; 31: 7-12
- Human interleukin 2.Methods Enzymol. 1985; 116: 493-525
- Detection of human IL-2 in normal and inflamed dental pulps.J Endod. 1997; 23: 366-370
- T lymphocyte subpopulations and interleukin-2, interferon-γ, and interleukin-4 in rat pulpitis experimentally induced by specific bacteria.J Endod. 2002; 25: 202-205
- Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation.Arch Oral Biol. 1999; 44: 55-66
- Role of IL-2 and helper T-lymphocytes in limiting periapical pathosis.J Endod. 2006; 32: 24-29
- Differential regulation of interleukin-10 production by genetic and environmental factors—a twin study.Genes Immun. 2002; 3: 407-413
- Gender differences in cytokine secretion by human peripheral blood mononuclear cells: role of estrogen in modulating LPS-induced cytokine secretion in an ex vivo septic model.Shock. 2001; 16: 340-343
- Plasma total antioxidant capacity in hemodialyzed patients and its relationship to other biomarkers of oxidative stress and lipid peroxidation.Clin Chem Lab Med. 2002; 40: 104-110
- The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases.Trends Pharmacol Sci. 2003; 24: 471-478
- Oxidative stress and vascular disease.Arterioscler Thromb Vasc Biol. 2005; 25: 29-38
- Redox modification of cell signaling in the cardiovascular system.J Mol Cell Cardiol. 2012; 52: 550-558
- Hydrogen peroxide and superoxide anion production by polymorphonuclear neutrophils in patients with chronic periapical granuloma, before and after surgical treatment.Clin Oral Investig. 2001; 5: 6-10
- Influence of endodontic treatment on systemic oxidative stress.Int J Med Sci. 2014; 11: 1-6
- Sex differences in oxidative stress biomarkers.Curr Drug Targets. 2014; 15: 811-815
- Effect of gender and sex hormones on vascular oxidative stress.Clin Exp Pharmacol Physiol. 2007; 34: 1037-1043
- Effects of ADMA upon gene expression: an insight into the pathophysiological significance of raised plasma ADMA.PLoS Med. 2005; 2: e264
- Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality: an intriguing interaction with diabetes mellitus.Diab Vasc Dis Res. 2010; 7: 105-118
- Inflammation is an important determinant of levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) in acute liver failure.Liver Transpl. 2007; 13: 400-405
- Role of asymmetric dimethylarginine in inflammatory reactions by angiotensin II.J Vasc Res. 2007; 44: 391-402
- Estrogen stimulates dimethylarginine dimethylaminohydrolase activity and the metabolism of asymmetric dimethylarginine.Circulation. 2003; 108: 1575-1580
- Can apical periodontitis modify systemic levels of inflammatory markers? A systematic review and meta-analysis.J Endod. 2013; 39: 1205-1217
- Genetic predisposition to persistent apical periodontitis.J Endod. 2011; 37: 455-459
Article info
Publication history
Published online: March 20, 2015
Identification
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© 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.
