|
1
|
Steigmann L, Kačarević ŽP, Khoury J, Nagy K, Feres M. Integration of precision medicine into the dental care setting. FRONTIERS IN DENTAL MEDICINE 2024; 5:1398897. [PMID: 39917647 PMCID: PMC11797757 DOI: 10.3389/fdmed.2024.1398897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 07/09/2024] [Indexed: 01/03/2025] Open
Abstract
This narrative review aims to discuss the incorporation of novel medical concepts and tools into dental practice, with the goal of improving early diagnosis and exploring new personalized treatment options for oral pathologies, such as caries and periodontitis. Preventative dental approaches concentrate on the timely detection of oral infections and the integration of biomarker analysis to recognize pathogenic changes at early stage of disease. Likewise, periodic monitoring after the treatment is relevant to ensure the balance in the oral biofilms and prevent relapse. Additionally, more attention has shifted towards the contributing factors to disease development, such as essential nutrients. Sufficient levels of vitamin C, vitamin D and zinc pre- and post-operatively are employed to boost immune function and reduce the risk of postoperative infections. Omega-3 fatty acids, melatonin, and antioxidants like vitamin E, which have anti-inflammatory properties, are utilized to help minimize excessive inflammation and promote faster recovery. The data presented in this manuscript emphasize the crucial integration of innovative healthcare concepts and tools into dental practices. By adopting a more holistic view of the patient, clinicians can tailor treatments to each individual's predispositions, lifestyle, and oral health conditions. This review also highlights the potential of salivary biomarkers and point-of-care technologies in enhancing early diagnostic accuracy and personalizing treatment. Bridging the gap between oral and systemic health is the most effective approach to improving patient quality of life. These findings underscore the importance of continued interdisciplinary collaboration in dentistry.
Collapse
Affiliation(s)
- Larissa Steigmann
- Department of Oral Medicine, Infection, and Immunity, Division of Periodontology, Harvard School of Dental Medicine, Boston, MA, United States
| | - Željka Perić Kačarević
- Department of Anatomy, Histology, Embryology, Pathology Anatomy and Pathology Histology, Faculty of Dental Medicine and Health Osijek, J.J. Strossmayer University of Osijek, Osijek, Croatia
| | - Jessica Khoury
- Department of Oral Biology, The Goldschleger School of Dental Medicine, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Katalin Nagy
- Department of Oral Surgery, Faculty of Dentistry, University of Szeged, Szeged, Hungary
| | - Magda Feres
- Department of Oral Medicine, Infection, and Immunity, Division of Periodontology, Harvard School of Dental Medicine, Boston, MA, United States
| |
Collapse
|
|
2
|
Fujiyoshi A, Kohsaka S, Hata J, Hara M, Kai H, Masuda D, Miyamatsu N, Nishio Y, Ogura M, Sata M, Sekiguchi K, Takeya Y, Tamura K, Wakatsuki A, Yoshida H, Fujioka Y, Fukazawa R, Hamada O, Higashiyama A, Kabayama M, Kanaoka K, Kawaguchi K, Kosaka S, Kunimura A, Miyazaki A, Nii M, Sawano M, Terauchi M, Yagi S, Akasaka T, Minamino T, Miura K, Node K. JCS 2023 Guideline on the Primary Prevention of Coronary Artery Disease. Circ J 2024; 88:763-842. [PMID: 38479862 DOI: 10.1253/circj.cj-23-0285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Affiliation(s)
| | - Shun Kohsaka
- Department of Cardiology, Keio University School of Medicine
| | - Jun Hata
- Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University
| | - Mitsuhiko Hara
- Department of Health and Nutrition, Wayo Women's University
| | - Hisashi Kai
- Department of Cardiology, Kurume Univeristy Medical Center
| | | | - Naomi Miyamatsu
- Department of Clinical Nursing, Shiga University of Medical Science
| | - Yoshihiko Nishio
- Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
| | - Masatsune Ogura
- Department of General Medical Science, Chiba University School of Medicine
- Department of Metabolism and Endocrinology, Eastern Chiba Medical Center
| | - Masataka Sata
- Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences
| | | | - Yasushi Takeya
- Division of Helath Science, Osaka University Gradiate School of Medicine
| | - Kouichi Tamura
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine
| | | | - Hiroshi Yoshida
- Department of Laboratory Medicine, The Jikei University Kashiwa Hospital
| | - Yoshio Fujioka
- Division of Clinical Nutrition, Faculty of Nutrition, Kobe Gakuin University
| | | | - Osamu Hamada
- Department of General Internal Medicine, Takatsuki General Hospital
| | | | - Mai Kabayama
- Division of Health Sciences, Osaka University Graduate School of Medicine
| | - Koshiro Kanaoka
- Department of Medical and Health Information Management, National Cerebral and Cardiovascular Center
| | - Kenjiro Kawaguchi
- Division of Social Preventive Medical Sciences, Center for Preventive Medical Sciences, Chiba University
| | | | | | | | - Masaki Nii
- Department of Cardiology, Shizuoka Children's Hospital
| | - Mitsuaki Sawano
- Department of Cardiology, Keio University School of Medicine
- Yale New Haven Hospital Center for Outcomes Research and Evaluation
| | | | - Shusuke Yagi
- Department of Cardiovascular Medicine, Tokushima University Hospital
| | - Takashi Akasaka
- Department of Cardiovascular Medicine, Nishinomiya Watanabe Cardiovascular Cerebral Center
| | - Tohru Minamino
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Meidicine
| | - Katsuyuki Miura
- Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science
| | - Koichi Node
- Department of Cardiovascular Medicine, Saga University
| |
Collapse
|
|
3
|
Swilem ES, Elkenany NM, Algazzar AS, Youssef N, Swilem SS, Gendia EA, Swillem AS, Elmalah AA, Sabah Z, Rasool T. The Impact of Periodontal Inflammation on the Severity of Coronary Atherosclerosis. Cureus 2024; 16:e57653. [PMID: 38707087 PMCID: PMC11070142 DOI: 10.7759/cureus.57653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2024] [Indexed: 05/07/2024] Open
Abstract
Introduction Through plausible biological mechanisms, periodontitis causes systemic inflammatory burden and response, thus resulting in damage far beyond the oral cavity. Studies have demonstrated periodontitis to be a significant risk factor for coronary heart disease (CHD) and stroke. The larger the quantum of periodontal inflamed tissue, the greater the chances of periodontitis eliciting bacteremia and systemic inflammatory responses. Studies have reported that periodontitis and other common oral infections play an important role in the development of atherosclerosis. Therefore, the quantity of inflamed periodontal tissue assumes significance in determining the severity of atherosclerosis. Hence, this study investigates the impact of periodontal inflamed surface area (PISA) on the severity of coronary atherosclerosis. Materials and methods In this cross-sectional study, a total of 160 patients who presented at the department of periodontics of The British University in Egypt (BUE) from 1 January 2023 to 30 September 2023 were enrolled. Patients were only enrolled if they had undergone coronary angiography within the last six months, were less than 60 years of age, shared their previous medical history and coronary angiographic report, and gave informed written consent. Data on classic coronary risk factors and periodontal inflammatory status and angiographic findings were recorded and subjected to appropriate statistical analysis. Results The results revealed that the periodontal inflamed surface area (p = 0.002) apart from age (p < 0.047) and low-density lipoprotein cholesterol (LDL-C) (p < 0.001) is a significant independent predictor of the severity of coronary atherosclerosis. Conclusions The periodontal inflamed surface area is an independent predictor of the severity of coronary atherosclerosis.
Collapse
Affiliation(s)
- Esraa S Swilem
- Faculty of Dental Medicine, The British University in Egypt, Cairo, EGY
| | - Nasima M Elkenany
- Department of Cardiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, EGY
| | - Alaa S Algazzar
- Department of Cardiology, Ahmed Maher Teaching Hospital, Cairo, EGY
| | - Nesma Youssef
- Faculty of Dental Medicine, Al-Azhar University, Cairo, EGY
| | - Sara S Swilem
- Faculty of Dental Medicine, The British University in Egypt, Cairo, EGY
| | - Eslam A Gendia
- Faculty of Dental Medicine, The British University in Egypt, Cairo, EGY
| | - Ahmad S Swillem
- Faculty of Dental Medicine, The British University in Egypt, Cairo, EGY
| | - Abeer A Elmalah
- Faculty of Medicine for Girls, Al-Azhar University, Cairo, EGY
| | - Zia Sabah
- Department of Medicine, King Khalid University, Abha, SAU
| | - Tariq Rasool
- Department of Medical Education and Simulation, University Institute of Computing, Chandigarh University, Chandigarh, IND
| |
Collapse
|
|
4
|
Sato A, Arai S, Sumi K, Fukamachi H, Miyake S, Ozawa M, Myers M, Maruoka Y, Shimizu K, Mizutani T, Kuwata H. Metagenomic Analysis of Bacterial Microflora in Dental and Atherosclerotic Plaques of Patients With Internal Carotid Artery Stenosis. CLINICAL MEDICINE INSIGHTS-CARDIOLOGY 2024; 18:11795468231225852. [PMID: 38328472 PMCID: PMC10848802 DOI: 10.1177/11795468231225852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 12/22/2023] [Indexed: 02/09/2024]
Abstract
Background Internal carotid artery stenosis is primarily attributed to atherosclerosis in the carotid artery bifurcation. Previous studies have detected oral bacteria in atherosclerotic lesions, suggesting an association between oral bacteria and atherosclerosis. In this study, we compared the bacterial flora of the atherosclerotic plaque in the carotid artery and dental plaque of patients with internal carotid artery stenosis using 16S ribosomal RNA (16S rRNA) metagenomic sequencing. Methods Fifty-four patients who underwent internal carotid endarterectomy for internal carotid artery stenosis at the Showa University Hospital between April 2016 and February 2018 were included. Polymerase chain reaction targeting the 16S rRNA gene detected bacterial DNA in the carotid plaques of 11 cases, of which only 5 could be further analyzed. Thereafter, DNA extracted from the carotid and oral plaques of these 5 cases were analyzed using metagenomic sequencing targeting 16S rRNA. In addition, their general condition and oral conditions were evaluated. The patients were classified into symptomatic and asymptomatic groups based on the presence or absence of symptoms of transient ischemic attack, and their bacterial flora was evaluated. Results The results demonstrated that the microflora of carotid plaques (n = 5) contained bacterial species from 55 families and 78 genera. In addition, 86.5% of the bacteria detected in the carotid plaques were also detected in oral plaques. Cariogenic and periodontopathic bacteria accounted for 27.7% and 4.7% of the bacteria in the carotid plaques, respectively. Conclusions These results suggest that oral bacteria are directly or indirectly involved in the pathogenesis of atherosclerosis. More extensive studies of oral commensal bacteria detected in extra-oral lesions are warranted to comprehensively investigate the role of oral bacteria in the pathogenesis of systemic diseases.
Collapse
Affiliation(s)
- Ayako Sato
- Department of Special Needs Dentistry, Division of Community-Based Comprehensive Dentistry, Showa University, Ohta-ku, Tokyo, Japan
- Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, Shinagawa-Ku, Tokyo, Japan
| | - Shintaro Arai
- Department of Neurosurgery, School of Medicine, Showa University, Shinagawa-Ku, Tokyo, Japan
| | - Kenji Sumi
- Department of Neurosurgery, School of Medicine, Showa University, Shinagawa-Ku, Tokyo, Japan
| | - Haruka Fukamachi
- Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, Shinagawa-Ku, Tokyo, Japan
| | - Satoko Miyake
- Department of Special Needs Dentistry, Division of Community-Based Comprehensive Dentistry, Showa University, Ohta-ku, Tokyo, Japan
| | - Manami Ozawa
- Department of Advanced Oral Surgery, Yokohama Clinic, Kanagawa Dental University, Yokohama, Kanagawa, Japan
| | - Mie Myers
- Department of Special Needs Dentistry, Division of Community-Based Comprehensive Dentistry, Showa University, Ohta-ku, Tokyo, Japan
| | - Yasubumi Maruoka
- Department of Special Needs Dentistry, Division of Community-Based Comprehensive Dentistry, Showa University, Ohta-ku, Tokyo, Japan
- Department of Oral and Maxillofacial Surgery, Totsuka Kyouritsu Daini Hospital, Yokohama-shi, Kanagawa, Japan
| | - Katsuyoshi Shimizu
- Department of Neurosurgery, School of Medicine, Showa University, Shinagawa-Ku, Tokyo, Japan
| | - Tohru Mizutani
- Department of Neurosurgery, School of Medicine, Showa University, Shinagawa-Ku, Tokyo, Japan
| | - Hirotaka Kuwata
- Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, Shinagawa-Ku, Tokyo, Japan
| |
Collapse
|
|
5
|
Barbosa De Accioly Mattos M, Bernardo Peixoto C, Geraldo de Castro Amino J, Cortes L, Tura B, Nunn M, Giambiagi-deMarval M, Sansone C. Coronary atherosclerosis and periodontitis have similarities in their clinical presentation. FRONTIERS IN ORAL HEALTH 2024; 4:1324528. [PMID: 38292927 PMCID: PMC10825671 DOI: 10.3389/froh.2023.1324528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 12/26/2023] [Indexed: 02/01/2024] Open
Abstract
Background Periodontitis (PE) and coronary heart disease (CHD) possess multiple mechanisms for a putative association. This case-control study compared the periodontal status among CHD subjects to controls without CHD, while also investigating atheroma invasion by known periodontal pathogens. Methods 161 subjects participated in this study were divided into three CHD groups: No CHD, chronic CHD, acute CHD. Additional analysis involved grouping subjects according to number of atheromas: no atheroma, 1-4 atheromas, 5-18 atheromas. Data were collected from medical records, periodontal examinations, and questionnaires that included demographic, behavioral, and oral health variables. Angiographic catheterizations were analyzed according to the number of atheroma lesions, lesion size, lesion location, and atheroma lesion stability. Lipoprotein profile, inflammatory markers and cells were analyzed. The microbiological branch added 30 individuals who had their atheroma lesion and subgingival plaque analyzed using polymerase chain reaction probes against the 16 s region, red complex and Aggregatibacter actinomycetemcomitans' DNA. Results Subjects with CHD had high levels of systemic inflammatory markers and low levels of high-density lipoproteins compared to subjects without CHD. Subjects without CHD and clear coronaries had a prevalence of mild CAL, while individuals with more atheroma lesions had advanced CAL and more active PE. Subjects with more advanced CAL were 4 times more likely to have CHD compared to subjects with less, which is comparable to smoking. Only 4 subjects had the screened pathogens detected in atheroma, although these subjects also have the screened pathogens in subgingival plaque. However, 80% of atheromas had bacteria. Conclusions CHD and PE showed similarities in progression while active PE led to more atheroma lesions that also tended to be larger in size.
Collapse
Affiliation(s)
- Marcelo Barbosa De Accioly Mattos
- School of Dentistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- Division of Periodontics, University of Kentucky College of Dentistry, Lexington, KY, United States
| | | | | | - Leandro Cortes
- Department of Cardiology, Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil
| | - Bernardo Tura
- Department of Cardiology, Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil
| | - Martha Nunn
- Department of Biostatistic, Nunn Biostatistical Solutions, Omaha, NE, United States
| | - Marcia Giambiagi-deMarval
- Instituto de Microbiologia Professor Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carmelo Sansone
- Departamento de Periodontia, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| |
Collapse
|
|
6
|
Alves LA, Naveed H, Franco EM, Garcia MT, Freitas VA, Junqueira JC, Bastos DC, Araujo TLS, Chen T, Mattos-Graner RO. PepO and CppA modulate Streptococcus sanguinis susceptibility to complement immunity and virulence. Virulence 2023; 14:2239519. [PMID: 37563831 PMCID: PMC10424592 DOI: 10.1080/21505594.2023.2239519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 07/12/2023] [Accepted: 07/15/2023] [Indexed: 08/12/2023] Open
Abstract
Streptococcus sanguinis is a ubiquitous commensal species of the oral cavity commonly involved as an opportunistic pathogen in cardiovascular infections. In this study, we investigated the functions of endopeptidase O (PepO) and a C3-degrading protease (CppA) in the systemic virulence of S. sanguinis. Isogenic mutants of pepO and cppA obtained in strain SK36 showed increased susceptibility to C3b deposition and to opsonophagocytosis by human polymorphonuclear neutrophils (PMN). These mutants differ, however, in their profiles of binding to serum amyloid P component (SAP) and C1q, whereas both showed reduced interaction with C4b-binding protein (C4BP) and/or factor H (FH) regulators as compared to SK36. The two mutants showed defects in ex vivo persistence in human blood, serum-mediated invasion of HCAEC endothelial cells, and virulence in a Galleria mellonella infection model. The transcriptional activities of pepO and cppA, assessed by RT-qPCR in nine wild-type strains, further indicated strain-specific profiles of pepO/cppA expression. Moreover, non-conserved amino acid substitutions were detected among the strains, mostly in CppA. Phylogenetic comparisons with homologues of streptococcal species of the oral and oropharyngeal sites suggested that S. sanguinis PepO and CppA have independent ancestralities. Thus, this study showed that PepO and CppA are complement evasion proteins expressed by S. sanguinis in a strain-specific manner, which are required for multiple functions associated with cardiovascular virulence.
Collapse
Affiliation(s)
- Lívia A. Alves
- Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, SP, Brazil
| | - Hassan Naveed
- Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, SP, Brazil
| | - Eduardo M. Franco
- Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, SP, Brazil
| | - Maíra Terra Garcia
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São José dos Campos, SP, Brazil
| | - Victor A. Freitas
- Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, SP, Brazil
| | - Juliana C. Junqueira
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São José dos Campos, SP, Brazil
| | - Débora C. Bastos
- Department of Biosciences, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, SP, Brazil
- Department of Cell Biology, São Leopoldo Mandic Medical School, Campinas, SP, Brazil
| | - Thaís L. S. Araujo
- Department of Biochemistry, Institute of Chemistry, University of São Paulo (USP), São Paulo, SP, Brazil
| | - Tsute Chen
- Department of Microbiology, The Forsyth Institute, Cambridge, MA, USA
| | - Renata O. Mattos-Graner
- Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, SP, Brazil
| |
Collapse
|
|
7
|
Patrakka O, Tuomisto S, Pienimäki J, Ollikainen J, Oksala N, Lampinen V, Ojanen MJT, Huhtala H, Hytönen VP, Lehtimäki T, Martiskainen M, Karhunen PJ. Thrombus Aspirates From Patients With Acute Ischemic Stroke Are Infiltrated by Viridans Streptococci. J Am Heart Assoc 2023; 12:e030639. [PMID: 37982253 PMCID: PMC10727284 DOI: 10.1161/jaha.123.030639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 10/27/2023] [Indexed: 11/21/2023]
Abstract
BACKGROUND Acute ischemic stroke may be due to embolism from ruptured atherosclerotic carotid arteries. DNA of oral bacteria, mainly the viridans streptococci group, has been detected in thrombus aspirates of patients with ischemic stroke as well as in carotid endarterectomy samples. Because viridans streptococci are known to possess thrombogenic properties, we studied whether their presence in thrombus aspirates and in carotid artery specimens can be confirmed using bacterial immunohistochemistry. METHODS AND RESULTS Thrombus aspirates from 61 patients with ischemic stroke (70.5% men; mean age, 66.8 years) treated with mechanical thrombectomy, as well as carotid endarterectomy samples from 20 symptomatic patients (65.0% men; mean age, 66.2 years) and 48 carotid artery samples from nonstroke autopsy cases (62.5% men; mean age, 66.4 years), were immunostained with an antibody cocktail against 3 species (Streptococcus sanguinis, Streptococcus mitis, and Streptococcus gordonii) of viridans streptococci. Of the thrombus aspirates, 84.8% were immunopositive for viridans streptococci group bacteria, as were 80.0% of the carotid endarterectomy samples, whereas immunopositivity was observed in 31.3% of the carotid artery samples from nonstroke autopsies. Most streptococci were detected inside neutrophil granulocytes, but there were also remnants of bacterial biofilm as well as free bacterial infiltrates in some samples. CONCLUSIONS Oral streptococci were found in aspirated thrombi of patients with acute ischemic stroke as well as in carotid artery samples. Our results suggest that viridans streptococci group bacteria may play a role in the pathophysiology of ischemic stroke.
Collapse
Affiliation(s)
- Olli Patrakka
- Department of Forensic Medicine, Faculty of Medicine and Health TechnologyTampere University and Fimlab LaboratoriesTampereFinland
| | - Sari Tuomisto
- Department of Forensic Medicine, Faculty of Medicine and Health TechnologyTampere University and Fimlab LaboratoriesTampereFinland
| | | | - Jyrki Ollikainen
- Department of NeurologyTampere University HospitalTampereFinland
| | - Niku Oksala
- Vascular CentreTampere University HospitalTampereFinland
- Surgery, Faculty of Medicine and Health TechnologyTampere UniversityTampereFinland
| | - Vili Lampinen
- Department of Forensic Medicine, Faculty of Medicine and Health TechnologyTampere University and Fimlab LaboratoriesTampereFinland
| | - Markus J. T. Ojanen
- Department of Forensic Medicine, Faculty of Medicine and Health TechnologyTampere University and Fimlab LaboratoriesTampereFinland
- Laboratory of Protein Dynamics, Faculty of Medicine and Health TechnologyTampere UniversityTampereFinland
| | - Heini Huhtala
- Faculty of Social SciencesTampere UniversityTampereFinland
| | - Vesa P. Hytönen
- Department of Forensic Medicine, Faculty of Medicine and Health TechnologyTampere University and Fimlab LaboratoriesTampereFinland
- Laboratory of Protein Dynamics, Faculty of Medicine and Health TechnologyTampere UniversityTampereFinland
| | - Terho Lehtimäki
- Department of Clinical Chemistry, Faculty of Medicine and Health TechnologyTampere University, Fimlab Laboratories and Finnish Cardiovascular Research Center TampereTampereFinland
| | - Mika Martiskainen
- Department of Forensic Medicine, Faculty of Medicine and Health TechnologyTampere University and Fimlab LaboratoriesTampereFinland
- National Institute for Health and WelfareHelsinkiFinland
| | - Pekka J. Karhunen
- Department of Forensic Medicine, Faculty of Medicine and Health TechnologyTampere University and Fimlab LaboratoriesTampereFinland
| |
Collapse
|
|
8
|
Xuan Y, Yu C, Ni K, Congcong L, Lixin Q, Qingxian L. Protective effects of tanshinone IIA on Porphyromonas gingivalis-induced atherosclerosis via the downregulation of the NOX2/NOX4-ROS mediation of NF-κB signaling pathway. Microbes Infect 2023; 25:105177. [PMID: 37392987 DOI: 10.1016/j.micinf.2023.105177] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 06/07/2023] [Accepted: 06/25/2023] [Indexed: 07/03/2023]
Abstract
Tanshinone IIA (TSA), an active component isolated from Danshen, possess high medicinal values against atherosclerosis by reducing vascular oxidative stress, inhibiting platelet aggregation, and protecting the endothelium from damage. The periodontal pathogen Porphyromonas gingivalis (P. gingivalis) has been proven to accelerate the development of atherosclerosis. We aim to determine the effects of TSA on P. gingivalis-induced atherosclerosis in ApoE-knockout (ApoE-/-) mice. After feeding with a high-lipid diet and infected with P. gingivalis three times per week for four weeks, TSA-treated (60 mg/kg/d) mice greatly inhibited atherosclerotic lesions both morphologically and biochemically and exhibited significantly reduction ROS, 8-OHdG, and ox-LDL levels in serum compared with P. gingivalis-infected mice. Additionally, TSA-treated mice were observed a marked reduction of ROS, 8-OHdG and ox-LDL in the serum, mRNA levels of COX-2, LOX-1, NOX2 and NOX4 in the aorta, as well as the levels of NOX2, NOX4, and NF-κB. These results suggest that TSA attenuates oxidative stress by decreasing NOX2 and NOX4 and downregulating NF-κB signaling pathway, which might be contributed to the amelioration of atherosclerosis.
Collapse
Affiliation(s)
- Yan Xuan
- Department of the Fourth Division, Peking University, School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China
| | - Cai Yu
- Department of Periodontology, Peking University, School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China
| | - Kang Ni
- Department of Periodontology, Peking University, School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China
| | - Lou Congcong
- Department of Periodontology, Peking University, School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China
| | - Qiu Lixin
- Department of the Fourth Division, Peking University, School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China.
| | - Luan Qingxian
- Department of Periodontology, Peking University, School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China.
| |
Collapse
|
|
9
|
Ono T. Number of Missing Teeth as a Surrogate Marker for Risk of Atherosclerotic Disease. J Atheroscler Thromb 2023; 30:1309-1310. [PMID: 37380441 PMCID: PMC10564644 DOI: 10.5551/jat.ed238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 05/13/2023] [Indexed: 06/30/2023] Open
Affiliation(s)
- Takahiro Ono
- Department of Geriatric Dentistry, Osaka Dental University, Osaka, Japan
| |
Collapse
|
|
10
|
Lattos A, Feidantsis K, Giantsis IA, Theodorou JA, Michaelidis B. Seasonality in Synergism with Multi-Pathogen Presence Leads to Mass Mortalities of the Highly Endangered Pinna nobilis in Greek Coastlines: A Pathophysiological Approach. Microorganisms 2023; 11:1117. [PMID: 37317091 DOI: 10.3390/microorganisms11051117] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/22/2023] [Accepted: 04/23/2023] [Indexed: 06/16/2023] Open
Abstract
Mortalities of Pinna nobilis populations set at risk the survival of the species from many Mediterranean coastline habitats. In many cases, both Haplosporidium pinnae and Mycobacterium spp. are implicated in mass mortalities of P. nobilis populations, leading the species into extinction. In the context of the importance of these pathogens' role in P. nobilis mortalities, the present study investigated two Greek populations of the species hosting different microbial loads (one only H. pinnae and the second both pathogens) by the means of pathophysiological markers. More specifically, the populations from Kalloni Gulf (Lesvos Island) and from Maliakos Gulf (Fthiotis), seasonally sampled, were chosen based on the host pathogens in order to investigate physiological and immunological biomarkers to assess those pathogens' roles. In order to determine if the haplosporidian parasite possesses a major role in the mortalities or if both pathogens are involved in these phenomena, a variety of biomarkers, including apoptosis, autophagy, inflammation and heat shock response were applied. The results indicated a decreased physiological performance of individuals hosting both pathogens in comparison with those hosting only H. pinnae. Our findings provide evidence for the synergistic role of those pathogens in the mortality events, which is also enhanced by the influence of seasonality.
Collapse
Affiliation(s)
- Athanasios Lattos
- Laboratory of Animal Physiology, Department of Zoology, Faculty of Science, School of Biology, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
| | - Konstantinos Feidantsis
- Laboratory of Animal Physiology, Department of Zoology, Faculty of Science, School of Biology, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
| | - Ioannis A Giantsis
- Department of Animal Science, Faculty of Agricultural Sciences, University of Western Macedonia, GR-53100 Florina, Greece
| | - John A Theodorou
- Department of Fisheries & Aquaculture, University of Patras, GR-23200 Mesolonghi, Greece
| | - Basile Michaelidis
- Laboratory of Animal Physiology, Department of Zoology, Faculty of Science, School of Biology, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
| |
Collapse
|
|
11
|
Prevalence of Microorganisms in Atherosclerotic Plaques of Coronary Arteries: A Systematic Review and Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:8678967. [PMID: 36506809 PMCID: PMC9731758 DOI: 10.1155/2022/8678967] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 07/05/2022] [Indexed: 12/02/2022]
Abstract
Background In this systematic review and meta-analysis, the existence of pathogens in atherosclerotic plaques of coronary arteries was investigated in coronary arteries diseases (CAD) patients. Methods This study was designed and implemented up to 31 August 2020. The findings present according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) checklist. Two independent reviewers (I.RJ and S.H) performed a comprehensive search on four different English databases including PubMed, ISI, Scopus, and Embase. In order to assess the quality of the articles, a checklist prepared by The Joanna Briggs Institute (JBI) was used. Results Finally, 44 studies were selected. The prevalence of different microorganisms in coronary arteries were as follows: Aggregatibacter actinomycetemcomitans (46.2%), Campylobacter rectus (43.0%), Chlamydia pneumonia (42.8%), Cytomegalovirus (29.1%), Helicobacter pylori (18.9%), Herpes simplex virus type 1 (5.9%), Porphyromonas gingivalis (42.6%), Prevotella intermedia (47.6%), Tannerella forsythia (43.7%), and Treponema denticola (32.9%). Conclusion Based on the result of this meta-analysis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans are the most common microorganisms in atherosclerotic plaques of coronary arteries and may have an important role in the development of atherosclerosis.
Collapse
|
|
12
|
Okahashi N, Nakata M, Kuwata H, Kawabata S. Oral mitis group streptococci: A silent majority in our oral cavity. Microbiol Immunol 2022; 66:539-551. [PMID: 36114681 DOI: 10.1111/1348-0421.13028] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 09/11/2022] [Accepted: 09/12/2022] [Indexed: 12/13/2022]
Abstract
Members of the oral mitis group streptococci including Streptococcus oralis, Streptococcus sanguinis, and Streptococcus gordonii are the most abundant inhabitants of human oral cavity and dental plaque, and have been implicated in infectious complications such as bacteremia and infective endocarditis. Oral mitis group streptococci are genetically close to Streptococcus pneumoniae; however, they do not produce cytolysin (pneumolysin), which is a key virulence factor of S. pneumoniae. Similar to S. pneumoniae, oral mitis group streptococci possess several cell surface proteins that bind to the cell surface components of host mammalian cells. S. sanguinis expresses long filamentous pili that bind to the matrix proteins of host cells. The cell wall-anchored nuclease of S. sanguinis contributes to the evasion of the neutrophil extracellular trap by digesting its web-like extracellular DNA. Oral mitis group streptococci produce glucosyltransferases, which synthesize glucan (glucose polymer) from sucrose of dietary origin. Neuraminidase (NA) is a virulent factor in oral mitis group streptococci. Influenza type A virus (IAV) relies on viral NA activity to release progeny viruses from infected cells and spread the infection, and NA-producing oral streptococci elevate the risk of IAV infection. Moreover, oral mitis group streptococci produce hydrogen peroxide (H2 O2 ) as a by-product of sugar metabolism. Although the concentrations of streptococcal H2 O2 are low (1-2 mM), they play important roles in bacterial competition in the oral cavity and evasion of phagocytosis by host macrophages and neutrophils. In this review, we intended to describe the diverse pathogenicity of oral mitis group streptococci.
Collapse
Affiliation(s)
- Nobuo Okahashi
- Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.,Center for Frontier Oral Science, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan
| | - Masanobu Nakata
- Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Hirotaka Kuwata
- Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan
| | - Shigetada Kawabata
- Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan
| |
Collapse
|
|
13
|
Farrugia C, Stafford GP, Gains AF, Cutts AR, Murdoch C. Fusobacterium nucleatum mediates endothelial damage and increased permeability following single species and polymicrobial infection. J Periodontol 2022; 93:1421-1433. [PMID: 35644006 PMCID: PMC9796848 DOI: 10.1002/jper.21-0671] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 04/04/2022] [Accepted: 05/20/2022] [Indexed: 01/07/2023]
Abstract
BACKGROUND Numerous lines of evidence link periodontal pathobionts and their virulence factors with endothelial damage. Most research has been conducted using single species infections at the exclusion of other periodontal microorganisms that have been identified in vascular tissue. Here, we assessed endothelial infection with either single or mixed periodontal species infection and examined their effect on endothelial damage and permeability. METHODS Cell surface abundance of platelet endothelial cell adhesion molecule-1 (PECAM-1) or endothelial permeability following infection with Porphyromonas gingivalis, Fusobacterium nucleatum subspecies (ssp) nucleatum, ssp polymorphum or Tannerella forsythia as single or mixed species infection was determined by flow cytometry and a fluorescent dextran permeability assay. Zebrafish embryos were infected systemically with either single or mixed species with mortality and disease measured over time. RESULTS F. nucleatum ssp nucleatum, ssp polymorphum and P. gingivalis significantly reduced PECAM-1 abundance in single species infection, whereas T. forsythia had no effect. F. nucleatum ssp polymorphum caused considerable mortality and morbidity in a zebrafish systemic infection model. Polymicrobial infection underscored the virulence of F. nucleatum ssp polymorphum in particular with increased endothelial cell death and reduced PECAM-1 abundance in co-infection studies with this organism. When injected systemically into zebrafish in polymicrobial infection, fluorescently labeled bacteria were distributed throughout the vasculature and cardiac region where, in some instances, they co-localized with each other. CONCLUSIONS These data provide further evidence on the effects of F. nucleatum on endothelium adhesion molecule abundance and permeability while also highlighting the importance of performing polymicrobial infection to study the molecular mechanisms associated with periodontal pathogen-induced vascular damage.
Collapse
Affiliation(s)
- Cher Farrugia
- School of Clinical DentistryUniversity of SheffieldSheffieldUK,Bristol Dental SchoolUniversity of BristolBristolUK
| | | | - Ashley F. Gains
- School of Clinical DentistryUniversity of SheffieldSheffieldUK
| | | | - Craig Murdoch
- School of Clinical DentistryUniversity of SheffieldSheffieldUK
| |
Collapse
|
|
14
|
Rughwani RR, Cholan PK, Victor DJ. Congenital Heart Diseases and Periodontal Diseases-Is There a Link? Front Cardiovasc Med 2022; 9:937480. [PMID: 35845078 PMCID: PMC9279652 DOI: 10.3389/fcvm.2022.937480] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 05/30/2022] [Indexed: 11/14/2022] Open
Abstract
An understanding in the field of periodontal medicine explains the fact that the oral cavity serves as a niche for numerous pathogenic microorganisms. When these microorganisms or their by-products disseminate to the various parts of the body, they are capable of triggering diseases characterized by an altered host immune-inflammatory response in the anatomically distinct organ. This mechanism is reported in the propagation of cardiovascular diseases with respect to periodontal medicine. Abundant amount of literature suggests an association between atherosclerotic cardiovascular disease and periodontal diseases. However, there is very less data available to highlight the association between periodontal disease and non-atherosclerotic cardiovascular disease, such as congenital anomalies of the heart. This review outlines the relationship between periodontal diseases and congenital heart diseases and also helps us understand whether the presence of periodontal disease can worsen the preexisting congenital cardiac disease.
Collapse
Affiliation(s)
- Roshan R. Rughwani
- Department of Periodontics and Oral Implantology, SRM Dental College, Chennai, India
| | | | | |
Collapse
|
|
15
|
Ding L, You Q, Jiang Q, Cao S, Jiang S. Meta-analysis of the association between periodontal disease, periodontal treatment and carotid intima-media thickness. J Periodontal Res 2022; 57:690-697. [PMID: 35700316 DOI: 10.1111/jre.13006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 04/12/2022] [Accepted: 05/10/2022] [Indexed: 11/28/2022]
Abstract
Periodontal disease is a major threat to oral health and would further contribute to systemic diseases without timely control. We aimed to evaluate the relation between periodontal disease, periodontal treatment and carotid intima-media thickness (CIMT) based on available epidemiological and clinical evidence. PubMed and Scopus were searched for relevant studies through May 2021. Observational studies reporting risk estimates with 95% confidence intervals (95% CIs) for the association between periodontal disease (including periodontitis and gingivitis) and risk of increased CIMT (defined as CIMT value that exceeded the cut-off value of clinical and prognostic significance), as well as interventional studies providing mean values with standard deviations of CIMT before and after periodontal intervention, were included. Random-effect models for meta-analysis were used to calculate the summary effect estimates with 95% CIs. A total of 406 citations were retrieved from electronic databases and 45 full-text articles were screened, leaving 11 articles using ultrasound to measure CIMT with 8744 participants included. Pooled results of seven cross-sectional studies involving 8558 participants indicated that compared to those without periodontitis, patients with periodontitis and those with severe periodontitis had an odds ratio of 1.42 (95% CI: 1.16, 1.75) and 1.70 (95% CI: 1.24, 2.33) for increased CIMT, respectively. Although publication bias was detected in these results, odds ratios corrected by the trim-and-fill method were still statistically significant. Results of four non-randomized controlled trials with 186 patients suggested that periodontal intervention may help reduce CIMT in patients with periodontal disease in the short term. Periodontitis, especially severe periodontitis, was significantly associated with the risk of increased CIMT. Periodontal intervention might help slow the progression of carotid intima-media thickening in patients with periodontal disease in the short term.
Collapse
Affiliation(s)
- Lifang Ding
- Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Qiqi You
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qingqing Jiang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shiyi Cao
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shengjun Jiang
- Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, China
| |
Collapse
|
|
16
|
Eberhard J. THE CONSISTENT DETECTION OF ORAL BACTERIA IN ATHEROSCLEROTIC PLAQUE DOES NOT QUALIFY FOR DENTAL TREATMENT TO REDUCE CARDIOVASCULAR RISK. J Evid Based Dent Pract 2022; 22:101718. [PMID: 35718428 DOI: 10.1016/j.jebdp.2022.101718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION Joshi, Chaitanya; Bapat, Ranjeet; Anderson, William; Joshi, Chaitanya; Bapat, Ranjeet; Anderson, William; Dawson, Dana; Hijazi, Karolin; Cherukara, George (2021). "Detection of periodontal microorganisms in coronary atheromatous plaque specimens of myocardial infarction patients: A systematic review and meta-analysis." Trends in Cardiovascular Medicine 31(1): 69-82. SOURCE OF FUNDING None. TYPE OF STUDY/DESIGN Systematic review with meta-analysis of data.
Collapse
|
|
17
|
Pierce G, Deniset J, Resch C, Mourin M, Dibrov E, Dibrov P. The evidence for a role of bacteria and viruses in cardiovascular disease. SCRIPTA MEDICA 2022. [DOI: 10.5937/scriptamed53-37418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Inflammation plays a critical role in atherosclerosis and cardiovascular disease. Bacteria and viruses are major causative agents of inflammation in the body which normally develops as a response to infection. It is a logical extention, therefore, to believe bacterial and viral infections may be involved in a variety of presentations of cardiovascular diseases. The purpose of this review is to describe the data and conclusions to date on the involvement of these infectious agents in the induction of cardiovascular disease. The review also discusses the various specific bacteria and viruses that have been implicated in cardiovascular disease and the mechanisms, if known, that these agents induce cardiovascular disease.
Collapse
|
|
18
|
Sasaki M, Shimoyama Y, Kodama Y, Ishikawa T. Tryptophanyl tRNA Synthetase from Human Macrophages Infected by Porphyromonas gingivalis Induces a Proinflammatory Response Associated with Atherosclerosis. Pathogens 2021; 10:1648. [PMID: 34959604 PMCID: PMC8708850 DOI: 10.3390/pathogens10121648] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 12/15/2021] [Accepted: 12/19/2021] [Indexed: 11/16/2022] Open
Abstract
Porphyromonas gingivalis is the most common microorganism associated with adult periodontal disease, causing inflammation around the subgingival lesion. In this study, we investigated tryptophanyl tRNA synthase (WRS) production by THP-1 cells infected with P. gingivalis. Cytokine production, leukocyte adhesion molecules, and low-density lipoprotein receptor (LDLR) expressions in cultured cells were examined. WRS was detected in THP-1 cell culture supernatants stimulated with P. gingivalis from 1 to 24 h, and apparent production was observed after 4 h. No change in WRS mRNA expression was observed from 1 to 6 h in THP-1 cells, whereas its expression was significantly increased 12 h after stimulation with P. gingivalis. Lactate dehydrogenase (LDH) activity was observed from 4 to 24 h. The TNF-α, IL-6, IL-8, and CXCL2 levels of THP-1 cells were upregulated after treatment with recombinant WRS (rWRS) and were significantly reduced when THP-1 cells were treated with C29. The MCP-1, ICAM-1, and VCAM-1 levels in human umbilical vein endothelial cells were upregulated following treatment with rWRS, and TAK242 suppressed these effects. Additionally, unmodified LDLR, macrophage scavenger receptor A, and lectin-like oxidized LDLRs were upregulated in THP-1 cells treated with rWRS. These results suggest that WRS from macrophages infected with P. gingivalis is associated with atherosclerosis.
Collapse
Affiliation(s)
- Minoru Sasaki
- Department of Microbiology, Division of Molecular Microbiology, Iwate Medical University, Morioka 028-3694, Japan; (Y.S.); (Y.K.); (T.I.)
| | | | | | | |
Collapse
|
|
19
|
Association between Oral Pathology, Carotid Stenosis, and Oral Bacterial DNA in Cerebral Thrombi of Patients with Stroke. Stroke Res Treat 2021; 2021:5402764. [PMID: 34531969 PMCID: PMC8440111 DOI: 10.1155/2021/5402764] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 08/17/2021] [Indexed: 12/02/2022] Open
Abstract
Methods Thrombus aspirates and control arterial blood were taken from 71 patients (70.4% male; mean age, 67.4 years) with acute ischemic stroke. Tooth pathology was registered using CT scans. Carotid stenosis was estimated with CTA and ultrasonography. The presence of bacterial DNA from aspirated thrombi was determined using quantitative PCR. We also analyzed the presence of these bacterial DNAs in carotid endarterectomies from patients with peripheral arterial disease. Results Bacterial DNA was found in 59 (83.1%) of the thrombus aspirates (median, 8.6-fold). Oral streptococcal DNA was found in 56 (78.9%) of the thrombus aspirates (median, 5.1-fold). DNA from A. actinomycetemcomitans and P. gingivalis was not found. Most patients suffered from poor oral health and had in median 19.0 teeth left. Paradoxically, patients with better oral health had more oral streptococcal DNA in their thrombus than the group with the worst pathology (p = 0.028). There was a trend (OR 7.122; p = 0.083) in the association of ≥50% carotid artery stenosis with more severe dental pathology. Oral streptococcal DNA was detected in 2/6 of carotid endarterectomies. Conclusions Stroke patients had poor oral health which tended to associate with their carotid artery stenosis. Although oral streptococcal DNA was found in thrombus aspirates and carotid endarterectomy samples, the amount of oral streptococcal DNA in thrombus aspirates was the lowest among those with the most severe oral pathology. These results suggest that the association between poor oral health and acute ischemic stroke is linked to carotid artery atherosclerosis.
Collapse
|
|
20
|
Liu K, Sun J, Shao L, He H, Liu Q, Li Y, Ge H. Correlation of periodontal diseases with intracranial aneurysm formation: novel predictive indicators. Chin Neurosurg J 2021; 7:31. [PMID: 34092261 PMCID: PMC8182916 DOI: 10.1186/s41016-021-00249-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 05/13/2021] [Indexed: 12/02/2022] Open
Abstract
Background We investigated whether periodontal diseases, specifically, periodontitis and gingivitis, could be risk factors of the incidence of intracranial aneurysms (IAs). Methods We performed a case–control study to compare the differences in the periodontal disease parameters of 281 cases that were divided into the IAs group and non-IAs group. All cases underwent complete radiographic examination for IAs and examination for periodontal health. Results Comparing with those in the non-IAs group, the cases in the IAs group were older (53.95 ± 8.56 vs 47.79 ± 12.33, p < 0.001) and had a higher incidence of hypertension (76 vs 34, p = 0.006). Univariate logistic regression analysis revealed that age (> 50 years) and hypertension were predictive risk factors of aneurysm formation (odds ratio [OR] 1.047, 95% confidence interval [95% CI] 1.022–1.073, p < 0.001 and OR 2.047, 95% CI 1.232–3.401, p = 0.006). In addition, univariate and multivariate logistic regression analyses showed that the parameters of periodontal diseases, including gingival index, plaque index, clinical attachment loss, and alveolar bone loss, were significantly associated with the occurrence of IAs (all p < 0.05). For further statistical investigation, the parameters of periodontal diseases were divided into four layers based on the quartered data. Poorer periodontal health condition (especially gingival index > 1.1 and plaque index > 1.5) had the correlation with IAs formation (p = 0.007 and p < 0.001). Conclusion Severe gingivitis or periodontitis, combining with hypertension, is significantly associated with the incidence of IAs.
Collapse
Affiliation(s)
- Keyun Liu
- Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, No. 119, West Road of South Fourth Ring, Fengtai, Beijing, 100070, People's Republic of China
| | - Jia Sun
- Department of Stomatology, Tianjin Stomatological Hospital, Hospital of Stomatology, Nankai University, Tianjin, 300041, People's Republic of China
| | - Lingling Shao
- Department of Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, People's Republic of China
| | - Hongwei He
- Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, No. 119, West Road of South Fourth Ring, Fengtai, Beijing, 100070, People's Republic of China
| | - Qinglin Liu
- Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, No. 119, West Road of South Fourth Ring, Fengtai, Beijing, 100070, People's Republic of China
| | - Youxiang Li
- Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, No. 119, West Road of South Fourth Ring, Fengtai, Beijing, 100070, People's Republic of China.
| | - Huijian Ge
- Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, No. 119, West Road of South Fourth Ring, Fengtai, Beijing, 100070, People's Republic of China.
| |
Collapse
|
|
21
|
Fernandes Forte CP, Oliveira FAF, Lopes CDB, Alves APNN, Mota MRL, de Barros Silva PG, Montenegro RC, Campos Ribeiro Dos Santos ÂK, Lobo Filho JG, Sousa FB. Streptococcus mutans in atherosclerotic plaque: Molecular and immunohistochemical evaluations. Oral Dis 2021; 28:1705-1714. [PMID: 33825326 DOI: 10.1111/odi.13869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 03/10/2021] [Accepted: 03/30/2021] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To verify the presence of Streptococcus mutans (S. mutans) in atherosclerotic plaque (AP) using techniques with different sensitivities, correlating with histological changes in plaque and immunoexpression of inflammatory markers. MATERIALS AND METHODS Thirteen AP samples were subjected to real-time polymerase chain reaction (qRT-PCR), histopathological analyses, histochemical analysis by Giemsa staining (GS), and immunohistochemical analysis for S. mutans, IL-1β, and TNF-α (streptavidin-biotin-peroxidase method). Ten necropsy samples of healthy vessels were used as controls. RESULTS All AP samples showed histopathological characteristics of severe atherosclerosis and were positive for S. mutans (100.0%) in qRT-PCR and immunohistochemical analyses. GS showed that Streptococcus sp. colonized the lipid-rich core regions and fibrous tissue, while the control group was negative for Streptococcus sp. IL-1β and TNF-α were expressed in 100% and 92.3% of the AP tested, respectively. The control samples were positive for S. mutans in qRT-PCR analysis, but negative for S. mutans, IL-1β, and TNF-α in immunohistochemical analyses. CONCLUSION The detection of S. mutans in AP and the visualization of Streptococcus sp. suggested a possible association between S. mutans and atherosclerosis. The results obtained from the control samples suggested the presence of DNA fragments or innocuous bacteria that were not associated with tissue alteration. However, future studies are necessary to provide more information.
Collapse
Affiliation(s)
| | | | - Camile de Barros Lopes
- Department of Human and Medical Genetics, School of Biological Sciences, Federal University of Para, Belém, Brazil
| | | | - Mário Rogério Lima Mota
- Department of Stomatology and Oral Pathology, School of Dentistry, Federal University of Ceará, Fortaleza, Brazil
| | | | - Raquel Carvalho Montenegro
- Department of Human Cytogenetics, School of Biological Sciences, Federal University of Para, Belém, Brazil
| | | | | | - Fabrício Bitu Sousa
- Department of Stomatology and Oral Pathology, School of Dentistry, Federal University of Ceará, Fortaleza, Brazil
| |
Collapse
|
|
22
|
Wadhawan A, Reynolds MA, Makkar H, Scott AJ, Potocki E, Hoisington AJ, Brenner LA, Dagdag A, Lowry CA, Dwivedi Y, Postolache TT. Periodontal Pathogens and Neuropsychiatric Health. Curr Top Med Chem 2021; 20:1353-1397. [PMID: 31924157 DOI: 10.2174/1568026620666200110161105] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 12/04/2019] [Accepted: 12/04/2019] [Indexed: 02/08/2023]
Abstract
Increasing evidence incriminates low-grade inflammation in cardiovascular, metabolic diseases, and neuropsychiatric clinical conditions, all important causes of morbidity and mortality. One of the upstream and modifiable precipitants and perpetrators of inflammation is chronic periodontitis, a polymicrobial infection with Porphyromonas gingivalis (P. gingivalis) playing a central role in the disease pathogenesis. We review the association between P. gingivalis and cardiovascular, metabolic, and neuropsychiatric illness, and the molecular mechanisms potentially implicated in immune upregulation as well as downregulation induced by the pathogen. In addition to inflammation, translocation of the pathogens to the coronary and peripheral arteries, including brain vasculature, and gut and liver vasculature has important pathophysiological consequences. Distant effects via translocation rely on virulence factors of P. gingivalis such as gingipains, on its synergistic interactions with other pathogens, and on its capability to manipulate the immune system via several mechanisms, including its capacity to induce production of immune-downregulating micro-RNAs. Possible targets for intervention and drug development to manage distal consequences of infection with P. gingivalis are also reviewed.
Collapse
Affiliation(s)
- Abhishek Wadhawan
- Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, United States.,Department of Psychiatry, Saint Elizabeths Hospital, Washington, D.C. 20032, United States
| | - Mark A Reynolds
- Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore 21201, United States
| | - Hina Makkar
- Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, United States
| | - Alison J Scott
- Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, United States
| | - Eileen Potocki
- VA Maryland Healthcare System, Baltimore VA Medical Center, Baltimore, United States
| | - Andrew J Hoisington
- Air Force Institute of Technology, Wright-Patterson Air Force Base, United States
| | - Lisa A Brenner
- Departments of Psychiatry, Neurology, and Physical Medicine & Rehabilitation, University of Colorado Anschutz Medical Campus, Aurora, United States.,Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Veterans Integrated Service Network (VISN) 19, Aurora, United States.,Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE), Aurora, United States
| | - Aline Dagdag
- Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, United States
| | - Christopher A Lowry
- Departments of Psychiatry, Neurology, and Physical Medicine & Rehabilitation, University of Colorado Anschutz Medical Campus, Aurora, United States.,Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Veterans Integrated Service Network (VISN) 19, Aurora, United States.,Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE), Aurora, United States.,Department of Integrative Physiology, Center for Neuroscience and Center for Microbial Exploration, University of Colorado Boulder, Boulder, United States.,Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Rocky Mountain Regional Veterans Affairs Medical Center (RMRVAMC), Aurora, United States
| | - Yogesh Dwivedi
- Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Alabama, United States
| | - Teodor T Postolache
- Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, United States.,Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Veterans Integrated Service Network (VISN) 19, Aurora, United States.,Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE), Aurora, United States.,Mental Illness Research, Education and Clinical Center (MIRECC), Veterans Integrated Service Network (VISN) 5, VA Capitol Health Care Network, Baltimore, United States
| |
Collapse
|
|
23
|
Wang Y, Lv F, Huang L, Zhang H, Li B, Zhou W, Li X, Du Y, Pan Y, Wang R. Human amnion-derived mesenchymal stem cells promote osteogenic differentiation of lipopolysaccharide-induced human bone marrow mesenchymal stem cells via ANRIL/miR-125a/APC axis. Stem Cell Res Ther 2021; 12:35. [PMID: 33413674 PMCID: PMC7791649 DOI: 10.1186/s13287-020-02105-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 12/14/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIM Periodontitis is a chronic inflammatory disease inducing the absorption of alveolar bone and leading to tooth loss. Human amnion-derived mesenchymal stem cells (HAMSCs) have been used for studying inflammatory processes. This study aimed to explore the role of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) in HAMSC-driven osteogenesis in lipopolysaccharide (LPS)-induced human bone marrow mesenchymal stem cells (HBMSCs). METHODS The cells were incubated with a co-culture system. Reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity were used to detect the oxidative stress level. Flow cytometry was performed to determine cell proliferation. The alkaline phosphatase (ALP) activity, Alizarin red assay, cell transfection, and rat mandibular defect model were used to evaluate the osteogenic differentiation. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, dual-luciferase reporter assay, and immunofluorescence staining were used to evaluate the molecular mechanisms. RESULTS This study showed that HAMSCs promoted the osteogenesis of LPS-induced HBMSCs, while the ANRIL level in HBMSCs decreased during co-culture. ANRIL had no significant influence on the proliferation of LPS-induced HBMSCs. However, its overexpression inhibited the HAMSC-driven osteogenesis in vivo and in vitro, whereas its knockdown reversed these effects. Mechanistically, this study found that downregulating ANRIL led to the overexpression of microRNA-125a (miR-125a), and further contributed to the competitive binding of miR-125a and adenomatous polyposis coli (APC), thus significantly activating the Wnt/β-catenin pathway. CONCLUSION The study indicated that HAMSCs promoted the osteogenic differentiation of LPS-induced HBMSCs via the ANRIL/miR-125a/APC axis, and offered a novel approach for periodontitis therapy.
Collapse
Affiliation(s)
- Yuli Wang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Fengyi Lv
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
| | - Lintong Huang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
| | - Hengwei Zhang
- Department of Pathology and Laboratory Medicine and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA
| | - Bing Li
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Weina Zhou
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Temporomandibular Joint, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Xuan Li
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
| | - Yifei Du
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China. .,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
| | - Yongchu Pan
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China. .,Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
| | - Ruixia Wang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China. .,Department of Dental Implant, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
| |
Collapse
|
|
24
|
Focal Infection and Periodontitis: A Narrative Report and New Possible Approaches. Int J Microbiol 2020; 2020:8875612. [PMID: 33488729 PMCID: PMC7803120 DOI: 10.1155/2020/8875612] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 09/29/2020] [Accepted: 10/17/2020] [Indexed: 12/13/2022] Open
Abstract
The "focal infection theory" is a historical concept based on the assumption that some infections may cause chronic and acute diseases in different districts of the body. Its great popularity spanned from 1930 to 1950 when, with the aim to remove all the foci of infection, drastic surgical interventions were performed. Periodontitis, a common oral pathology mainly of bacterial origin, is the most evident example of this phenomenon today: in fact, bacteria are able to migrate, develop and cause health problems such as cardiovascular and respiratory diseases, diabetes, and osteoporosis. The aim of this narrative report is to verify the hypothesis of the association between oral infections and systemic diseases by different ways of approach and, at the same time, to propose new kinds of treatment today made possible by technological progress. The analysis of the literature demonstrated a strong relationship between these conditions, which might be explained on the basis of the recent studies on microbiota movement inside the body. Prevention of the oral infections, as well as of the possible systemic implications, may be successfully performed with the help of new technologies, such as probiotics and laser.
Collapse
|
|
25
|
Patrakka O, Pienimäki JP, Tuomisto S, Ollikainen J, Lehtimäki T, Karhunen PJ, Martiskainen M. Oral Bacterial Signatures in Cerebral Thrombi of Patients With Acute Ischemic Stroke Treated With Thrombectomy. J Am Heart Assoc 2020; 8:e012330. [PMID: 31117858 PMCID: PMC6585368 DOI: 10.1161/jaha.119.012330] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background Chronic infections have been reported to be risk factors for both coronary heart disease and ischemic stroke. DNA of oral bacteria, mainly from the viridans streptococci group, has been detected in coronary thrombus aspirates of myocardial infarction and cerebral aneurysms. Viridans streptococci are known to cause infective endocarditis and possess thrombogenic properties. We studied the presence of oral bacterial DNA in thrombus aspirates of patients with acute ischemic stroke treated with mechanical thrombectomy. Methods and Results Thrombus aspirates and arterial blood were taken from 75 patients (69% men; mean age, 67 years) with acute ischemic stroke. The presence of Streptococcus species, mainly the Streptococcus mitis group, belonging to viridans streptococci as well as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in samples were determined using a quantitative polymerase chain reaction with specific primers and probes. The relative amount of bacterial DNA in a sample was determined with the comparative threshold cycle method. Bacterial DNA was detected in 84% (n=63) of aspired thrombi, and 16% (n=12) of samples were considered bacterial DNA negative. DNA of Streptococcus species, mainly the S mitis group, was found in 79% (n=59) of samples. The median relative amount of Streptococcus species DNA was 5.10‐fold higher compared with the control blood samples from the same patients. All thrombi were negative for both P gingivalis and A actinomycetemcomitans. Conclusions This is the first study showing the common presence of bacterial DNA from viridans streptococci in aspired thrombi of patients with acute ischemic stroke. Streptococcal bacteria, mostly of oral origin, may contribute to the progression and thrombotic events of cerebrovascular diseases.
Collapse
Affiliation(s)
- Olli Patrakka
- 1 Department of Forensic Medicine Faculty of Medicine and Health Technology Tampere University and Fimlab Laboratories Tampere Finland
| | - Juha-Pekka Pienimäki
- 2 Division of Interventional Radiology Department of Radiology Tampere University Hospital Tampere Finland
| | - Sari Tuomisto
- 1 Department of Forensic Medicine Faculty of Medicine and Health Technology Tampere University and Fimlab Laboratories Tampere Finland
| | - Jyrki Ollikainen
- 3 Department of Neurology Tampere University Hospital Tampere Finland
| | - Terho Lehtimäki
- 4 Department of Clinical Chemistry Faculty of Medicine and Health Technology Tampere University Fimlab Laboratories and Finnish Cardiovascular Research Center Tampere Finland
| | - Pekka J Karhunen
- 1 Department of Forensic Medicine Faculty of Medicine and Health Technology Tampere University and Fimlab Laboratories Tampere Finland
| | - Mika Martiskainen
- 1 Department of Forensic Medicine Faculty of Medicine and Health Technology Tampere University and Fimlab Laboratories Tampere Finland.,5 National Institute for Health and Welfare Helsinki Finland
| |
Collapse
|
|
26
|
Xuan Y, Cai Y, Wang XX, Shi Q, Qiu LX, Luan QX. [Effect of Porphyromonas gingivalis infection on atherosclerosis in apolipoprotein-E knockout mice]. BEIJING DA XUE XUE BAO. YI XUE BAN = JOURNAL OF PEKING UNIVERSITY. HEALTH SCIENCES 2020; 52. [PMID: 32773813 PMCID: PMC7433629 DOI: 10.19723/j.issn.1671-167x.2020.04.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 03/15/2023]
Abstract
OBJECTIVE Studies have indicated that periodontal pathogen Porphyromonas gingivalis (P. gingivalis) infection may contributed to accelerate the development of atherosclerosis. The aim of this study was to investigate the effect of inflammation, oxidative stress and the mechanism on atherosclerosis in apolipoprotein-E knockout (ApoE-/-) mice with P. gingivalis infection. METHODS Eight-week-old male ApoE-/- mice (C57BL/6) were maintained under specific pathogen-free conditions and fed regular chow and sterile water after 1 weeks of housing. The animals were randomly divided into two groups: (a) ApoE-/- + PBS (n=8); (b) ApoE-/- + P.gingivalis strain FDC381 (n=8). Both of the groups received intravenous injections 3 times per week for 4 weeks since 8 weeks of age. The sham control group received injections with phosphate buffered saline only, while the P. gingivalis-challenged group with P.gingivalis strain FDC381at the same time. After 4 weeks, oxidative stress mediators and inflammation cytokines were analyzed by oil red O in heart, Enzyme linked immunosorbent assay (ELISA) in serum, quantitative real-time PCR and Western blot in aorta. RESULTS In our study, we found accelerated development of atherosclerosis and plaque formation in aorta with oil red O staining, increased oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), NADPH oxidase (NOX)-2 and NOX-4], as well as increased inflammation cytokines [interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α)] in the serum and aorta of the P. gingivalis-infected ApoE-/- mice. Compared with the control group, there was a significant increase protein level of nuclear factor-kappa B (NF-κB) in aorta after P. gingivalis infection. CONCLUSIONS Our results suggest that chronic intravenous infection of P. gingivalis in ApoE-/- mice could accelerate the development of atherosclerosis by disturbing the lipid profile and inducing oxidative stress and inflammation. The NF-κB signaling pathway might play a potential role in the P. gingivalis-accelerated atherogenesis.
Collapse
Affiliation(s)
- Y Xuan
- Fourth Clinical Division, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Y Cai
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - X X Wang
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Q Shi
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - L X Qiu
- Fourth Clinical Division, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | | |
Collapse
|
|
27
|
Schenkein HA, Papapanou PN, Genco R, Sanz M. Mechanisms underlying the association between periodontitis and atherosclerotic disease. Periodontol 2000 2020; 83:90-106. [PMID: 32385879 DOI: 10.1111/prd.12304] [Citation(s) in RCA: 221] [Impact Index Per Article: 44.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Atherosclerosis is central to the pathology of cardiovascular diseases, a group of diseases in which arteries become occluded with atheromas that may rupture, leading to different cardiovascular events, such as myocardial infarction or ischemic stroke. There is a large body of epidemiologic and animal model evidence associating periodontitis with atherosclerotic disease, and many potential mechanisms linking these diseases have been elucidated. This chapter will update knowledge on these mechanisms, which generally fall into 2 categories: microbial invasion and infection of atheromas; and inflammatory and immunologic. With respect to the invasion and infection of atheromas, it is well established that organisms from the subgingival biofilm can enter the circulation and lodge in most distant tissues. Bacteremias resulting from oral interventions, and even oral hygiene activities, are well documented. More recently, indirect routes of entry of oral organisms (via phagocytes or dendritic cells) have been described for many oral organisms, into many tissues. Such organisms include the periodontal pathogens Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum. Intracellular survival of these organisms with dissemination to distant sites (The Trojan Horse approach) has been described. Their relative contribution to atheroma formation and progression has been studied mainly in experimental research, with results demonstrating that these organisms can invade endothelial cells and phagocytic cells within the atheroma, leading to pathogenic changes and progression of the atheroma lesion. The second category of mechanisms potentially linking periodontitis to atherosclerosis includes the dumping of inflammatory mediators originating from periodontal lesions into the systemic circulation. These inflammatory mediators, such as C-reactive protein, matrix metalloproteinases, fibrinogen, and other hemostatic factors, would further accelerate atheroma formation and progression, mainly through oxidative stress and inflammatory dysfunction. Moreover, direct effects on lipid oxidation have also been described. In summary, the evidence supports the concept that periodontitis enhances the levels of systemic mediators of inflammation that are risk factors for atherosclerotic diseases.
Collapse
Affiliation(s)
- Harvey A Schenkein
- Department of Periodontics, School of Dentistry, Virginia Commonwealth University, Richmond, Virginia
| | - Panos N Papapanou
- Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, Columbia University College of Dental Medicine, NewYork, New York, USA
| | - Robert Genco
- Departments of Oral Biology, and Microbiology and Immunology, Center for Microbiome Research, University at Buffalo, Buffalo, New York, USA
| | - Mariano Sanz
- ETEP (Etiology and Therapy of Periodontal Diseases) Research Group, University Complutense, Madrid, Spain
| |
Collapse
|
|
28
|
Beck JD, Papapanou PN, Philips KH, Offenbacher S. Periodontal Medicine: 100 Years of Progress. J Dent Res 2020; 98:1053-1062. [PMID: 31429666 DOI: 10.1177/0022034519846113] [Citation(s) in RCA: 148] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Periodontal medicine is a term used to describe how periodontal infection/inflammation may impact extraoral health. Periodontitis has been linked to over 50 systemic diseases and conditions. As part of the Journal of Dental Research's Centennial Celebration, this narrative review discusses periodontal medicine research done over the past 100 y, with particular focus on the effects of periodontal disease on 3 pathological conditions: cardiovascular disease, diabetes mellitus, and adverse pregnancy outcomes. We selected 29 total studies that were the "first" of their kind, as they provided novel observations or contributed to shifting paradigms as well as important studies that made strong contributions to progress in understanding relationships to the systemic conditions. These studies were organized in an overview timeline and broken down into timelines by topic: cardiovascular disease (n = 10), diabetes (n = 12), and adverse pregnancy outcomes (n = 7). Overall, the majority of cross-sectional, case-control, and longitudinal studies have revealed positive associations between poor periodontal status and cardiovascular disease, diabetes metabolic control, and a number of adverse pregnancy outcomes, and these associations are upheld in systematic reviews. Findings from randomized controlled trials testing the effects of periodontal therapy on systemic health outcomes were conflicting and inconsistent. While there has been a great deal of progress, we highlight lessons learned and make comments and suggestions on a number of key aspects, including the heterogeneity of case definitions of periodontal disease across studies, accounting for features of the periodontal phenotype that are most relevant to the biological link between periodontitis and systemic outcomes, the role of other comorbid inflammatory conditions, selection of study participants, and timing and intensity of the periodontal intervention.
Collapse
Affiliation(s)
- J D Beck
- 1 Department of Periodontology, University of North Carolina School of Dentistry, Chapel Hill, NC, USA
| | - P N Papapanou
- 2 Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, Columbia University College of Dental Medicine, New York City, NY, USA
| | - K H Philips
- 3 Department of Oral and Craniofacial Health Sciences, University of North Carolina School of Dentistry, Chapel Hill, NC, USA
| | - S Offenbacher
- 1 Department of Periodontology, University of North Carolina School of Dentistry, Chapel Hill, NC, USA
| |
Collapse
|
|
29
|
Yoshioka S, Miyamoto T, Satomi J, Tada Y, Yagi K, Shimada K, Naruishi K, Shikata E, Yamaguchi I, Yamaguchi T, Korai M, Okayama Y, Harada M, Kitazato KT, Kanematsu Y, Nagahiro S, Takagi Y. Disequilibrium of Plasma Protease/Anti-Protease Due to Severe Periodontal Disease Contributes to Human Subarachnoid Hemorrhage. NEUROSURGERY OPEN 2020. [DOI: 10.1093/neuopn/okaa007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
ABSTRACT
BACKGROUND
The pathophysiology of subarachnoid hemorrhages (SAHs) due to ruptured intracranial aneurysms (IAs) remains unclear. Although a relationship between SAHs and periodontal disease (PD) has been suggested, the mechanism requires clarification.
OBJECTIVE
To evaluate the relationship between PD and SAHs and to identify periodontal pathogens associated with SAHs.
METHODS
This prospective study included consecutive patients with ruptured (n = 11) and unruptured (n = 14) IAs and healthy controls (n = 8). The plasma and plaque subgingival bacterial deoxyribonucleic acid (DNA) levels in PD were evaluated by a dentist using the Community Periodontal Index of Treatment Needs (CPITN). Plasma levels of matrix metalloproteinase (MMP-9), tissue inhibitors of matrix metalloproteinase (TIMP2), and procollagen I were analyzed.
RESULTS
Patients with ruptured IAs, had significantly higher CPITN scores than the controls, suggesting that ruptured IAs were associated with severe PD. Although no rupture-specific bacteria were identified, the positive rate of plaque subgingival bacterial DNA was significantly higher in patients with severe PD than in those without severe PD. Multivariate logistic regression analysis indicated that bleeding on probing (BOP) was associated with ruptured IAs (odds ratio, 1.10; 95% confidence interval 1.04–1.20; P = .0001). BOP was positively associated with plasma MMP-9 levels and a disequilibrium in the MMP-9/TIMP2 ratio. BOP was negatively correlated with plasma procollagen I levels (P < .05, for each). This suggested that local inflammation with severe PD might have systemic effects and lead to ruptured IAs.
CONCLUSION
Disequilibrium of plasma protease/anti-protease associated with a high BOP rate in severe PD may be attributable to IA rupture.
Collapse
Affiliation(s)
- Shotaro Yoshioka
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Takeshi Miyamoto
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Junichiro Satomi
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Yoshiteru Tada
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Kenji Yagi
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Kenji Shimada
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Koji Naruishi
- Department of Periodontology and Endodontology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Eiji Shikata
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Izumi Yamaguchi
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Tadashi Yamaguchi
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Masaaki Korai
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Yoshihiro Okayama
- Clinical Trial Center, Tokushima University and Tokushima University Hospital, Tokushima, Japan
| | - Masafumi Harada
- Department of Radiology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Keiko T Kitazato
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Yasuhisa Kanematsu
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Shinji Nagahiro
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Yasushi Takagi
- Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| |
Collapse
|
|
30
|
Liu XR, Xu Q, Xiao J, Deng YM, Tang ZH, Tang YL, Liu LS. Role of oral microbiota in atherosclerosis. Clin Chim Acta 2020; 506:191-195. [DOI: 10.1016/j.cca.2020.03.033] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 03/21/2020] [Accepted: 03/23/2020] [Indexed: 02/08/2023]
|
|
31
|
Boyapati R, Vudathaneni V, Nadella SB, Ramachandran R, Dhulipalla R, Adurty C. Mapping the link between cardiac biomarkers and chronic periodontitis: A clinico-biochemical study. J Indian Soc Periodontol 2020; 24:309-315. [PMID: 32831502 PMCID: PMC7418541 DOI: 10.4103/jisp.jisp_417_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 01/23/2020] [Accepted: 03/22/2020] [Indexed: 12/15/2022] Open
Abstract
Background: Various risk factors are coupled with atherosclerotic complications, such as myocardial infarction and stroke. Periodontitis is considered one of them. Aims and Objectives: The objective of the study is to compare and correlate the occurrences of periodontitis with serum levels of cardiac-biomarkers in patients with coronary heart-disorders. Materials and Methods: Of 70 individuals diagnosed with coronary artery diseases, 32 patients with chronic periodontitis constituted the test group, 31 without chronic periodontitis constituted the control group. Cardiac-biomarkers analyzed were Troponin T, Troponin I, Myoglobin; low density lipoprotein (LDL), high-density lipoprotein, very LDL (VLDL), total cholesterol (TC), and highly sensitive C-reactive protein (Hs-CRP). Periodontal characteristics were drawn from the plaque index (PI) and gingival index, probing depth (PD), clinical attachment loss, and periodontal inflammatory surface area (PISA). Statistical Analysis: In order to separate any association between cardiac biomarkers and clinical parameters of periodontitis, detailed statistical analysis through independent t-test and Pearson test of correlation was done. Results: Statistically significant differences were seen not only in PI, PD, and PISA between both the groups (P < 0.05), but also between various cardiac parameters of test and control groups (P < 0.001). Positive relations were seen in the test group, between cardiac biomarkers such as TC, VLDL, Hs-CRP, and Troponin T with periodontal parameters such as PD and PISA. Conclusion: The study reveals, a strong association between periodontitis and diseases of cardiovascular nature, highlighting the need for awareness and timely medical interventions to prevent periodontitis from scaling up and interfering with the risk of cardiovascular problems.
Collapse
Affiliation(s)
- Ramanarayana Boyapati
- Department of Periodontics, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh, India
| | - Vijaya Vudathaneni
- Department of Internal Medicine, North Central Bronx Hospital, Bronx, New York, USA
| | | | | | - Ravindranath Dhulipalla
- Department of Periodontics, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh, India
| | - Chaitanya Adurty
- Department of Periodontics, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh, India
| |
Collapse
|
|
32
|
Abstract
Microbial contributions to the immunopathogenesis of autoimmune rheumatic diseases have been studied since the advent of germ theory in the 19th century. With the exception of Group A Streptococcus in rheumatic fever, early studies failed to establish causal relationships between specific pathobionts and rheumatic disease. Today, systemic autoimmune diseases are thought to result from a complex interplay of environmental factors, individual genetic risk, and stochastic events. Interactions of microbiota and the immune system have been shown to promote and sustain chronic inflammation and autoimmunity. In mechanistic studies, microbe-immune cell interactions have been implicated in the initiation of autoimmune rheumatic diseases, e.g., through the posttranslational modification of autoantigens in rheumatoid arthritis or through neutrophil cell death and cross-reactivity with commensal orthologs in systemic lupus erythematosus. In parallel, modern molecular techniques have catalyzed the study of the microbiome in systemic autoimmune diseases. Here, I review current insights gained into the skin, oral, gut, lung, and vascular microbiome in connective tissue diseases and vasculitis. Mechanism relevant to the development and propagation of autoimmunity will be discussed whenever explored. While studies on autoimmune rheumatic disease have almost invariably shown abnormal microbiome structure (dysbiosis), substantial variability in microbial composition between studies makes generalization difficult. Moreover, an etiopathogenic role of specific pathobionts cannot be inferred by association alone. Integrating descriptive studies of microbial communities with hypothesis-driven research informed by immunopathogenesis will be important in elucidating targetable mechanisms in preclinical and established rheumatic disease.
Collapse
Affiliation(s)
- Maximilian F Konig
- Division of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| |
Collapse
|
|
33
|
Graber K, Khan F, Glück B, Weigel C, Marzo S, Doshi H, Ehrhardt C, Heller R, Gräler M, Henke A. The role of sphingosine-1-phosphate signaling in HSV-1-infected human umbilical vein endothelial cells. Virus Res 2020; 276:197835. [DOI: 10.1016/j.virusres.2019.197835] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 12/06/2019] [Accepted: 12/06/2019] [Indexed: 01/14/2023]
|
|
34
|
Hashizume-Takizawa T, Yamaguchi Y, Kobayashi R, Shinozaki-Kuwahara N, Saito M, Kurita-Ochiai T. Oral challenge with Streptococcus sanguinis induces aortic inflammation and accelerates atherosclerosis in spontaneously hyperlipidemic mice. Biochem Biophys Res Commun 2019; 520:507-513. [DOI: 10.1016/j.bbrc.2019.10.057] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 10/05/2019] [Indexed: 12/11/2022]
|
|
35
|
Arnao V, Tuttolomondo A, Daidone M, Pinto A. Lipoproteins in Atherosclerosis Process. Curr Med Chem 2019; 26:1525-1543. [PMID: 31096892 DOI: 10.2174/0929867326666190516103953] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Revised: 11/17/2017] [Accepted: 12/10/2017] [Indexed: 01/15/2023]
Abstract
BACKGROUND Dyslipidaemias is a recognized risk factor for atherosclerosis, however, new evidence brought to light by trials investigating therapies to enhance HDLcholesterol have suggested an increased atherosclerotic risk when HDL-C is high. RESULTS Several studies highlight the central role in atherosclerotic disease of dysfunctional lipoproteins; oxidised LDL-cholesterol is an important feature, according to "oxidation hypothesis", of atherosclerotic lesion, however, there is today a growing interest for dysfunctional HDL-cholesterol. The target of our paper is to review the functions of modified and dysfunctional lipoproteins in atherogenesis. CONCLUSION Taking into account the central role recognized to dysfunctional lipoproteins, measurements of functional features of lipoproteins, instead of conventional routine serum evaluation of lipoproteins, could offer a valid contribution in experimental studies as in clinical practice to stratify atherosclerotic risk.
Collapse
Affiliation(s)
- Valentina Arnao
- BioNeC Dipartimento di BioMedicina Sperimentale e Neuroscienze Cliniche, Universita degli Studi di Palermo, Palermo, Italy.,PhD School of: Medicina Clinica e Scienze del Comportamento-Biomedical Department of Internal and Specialistic Medicine. (Di.Bi.M.I.S), University of Palermo, Palermo, Italy
| | - Antonino Tuttolomondo
- Internal Medicine and Stroke Care Ward, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties, (PROMISE), University of Palermo, Palermo, Italy
| | - Mario Daidone
- Internal Medicine and Stroke Care Ward, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties, (PROMISE), University of Palermo, Palermo, Italy
| | - Antonio Pinto
- Internal Medicine and Stroke Care Ward, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties, (PROMISE), University of Palermo, Palermo, Italy
| |
Collapse
|
|
36
|
The Role of the Microbiota in the Diabetic Peripheral Artery Disease. Mediators Inflamm 2019; 2019:4128682. [PMID: 31205450 PMCID: PMC6530226 DOI: 10.1155/2019/4128682] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 04/01/2019] [Accepted: 04/14/2019] [Indexed: 02/07/2023] Open
Abstract
Vascular complications of diabetes mellitus represent a major public health problem. Although many steps forward have been made to define the causes and to find the best possible therapies, the problem remains crucial. In recent years, more and more evidences have defined a link between microbiota and the initiation, promotion, and evolution of atherosclerotic disease, even in the diabetic scenario. There is an urgency to develop the knowledge of modern medicine about the link between gut microbiota and its host's metabolic pathways, and it would be useful to understand and justify the interindividual diversity of clinical disease presentation of diabetic vascular complication even if an optimization of pharmacological treatment has been made or in the case of young patients where hypertension, dyslipidemia, and diabetes are not able to justify a very quick progress of atherosclerotic process. The aim of the present review is to gather all the best available evidence in this regard and to define a new role of the microbiota in this field, from biomarker to possible therapeutic target.
Collapse
|
|
37
|
Alves LA, de Carli TR, Harth-Chu EN, Mariano FS, Höfling JF, Stipp RN, Mattos-Graner RO. Oral streptococci show diversity in resistance to complement immunity. J Med Microbiol 2019; 68:600-608. [PMID: 30843785 DOI: 10.1099/jmm.0.000955] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
PURPOSE Mechanisms underlying systemic infections by oral species of Mitis (Streptococcus mitis, Streptococcus oralis) and Sanguinis (Streptococcus gordonii, Streptococcus sanguinis) commensal streptococci are poorly understood. This study investigates profiles of susceptibility to complement-mediated host immunity in representative strains of these four species, which were isolated from oral sites or from the bloodstream. METHODOLOGY Deposition of complement opsonins (C3b/iC3b), and surface binding to C-reactive protein (CRP) and to IgG antibodies were quantified by flow cytometry in 34 strains treated with human serum (HS), and compared to rates of opsonophagocytosis by human PMN mediated by complement (CR1/3) and/or IgG Fc (FcγRII/III) receptors. RESULTS S. sanguinis strains showed reduced susceptibility to complement opsonization and low binding to CRP and to IgG compared to other species. Surface levels of C3b/iC3b in S. sanguinis strains were 4.5- and 7.8-fold lower than that observed in S. gordonii and Mitis strains, respectively. Diversity in C3b/iC3b deposition was evident among Mitis species, in which C3b/iC3b deposition was significantly associated with CR/FcγR-dependent opsonophagocytosis by PMN (P<0.05). Importantly, S. gordonii and Mitis group strains isolated from systemic infections showed resistance to complement opsonization when compared to oral isolates of the respective species (P<0.05). CONCLUSIONS This study establishes species-specific profiles of susceptibility to complement immunity in Mitis and Sanguinis streptococci, and indicates that strains associated with systemic infections have increased capacity to evade complement immunity. These findings highlight the need for studies identifying molecular functions involved in complement evasion in oral streptococci.
Collapse
Affiliation(s)
- Lívia A Alves
- Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil
| | - Thaís R de Carli
- Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil
| | - Erika N Harth-Chu
- Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil
| | - Flávia S Mariano
- Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil
| | - José F Höfling
- Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil
| | - Rafael N Stipp
- Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil
| | - Renata O Mattos-Graner
- Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil
| |
Collapse
|
|
38
|
Moeintaghavi A, Arab HR, Moghaddam MA, Shahmohammadi R, Bardan BY, Soroush Z. Evaluation of Effect of Surgical and Nonsurgical Periodontal Therapy on Serum C-Reactive Protein, Triglyceride, Cholesterol, Serum Lipoproteins and Fasting Blood Sugar in Patients with Severe Chronic Periodontitis. Open Dent J 2019. [DOI: 10.2174/1874210601913010015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Background:Cardiovascular disease has been associated with multiple risk factors such as dyslipidemia. However, the focus has recently shifted towards some novel risk factorsi.e. infection from periodontitis.Given this background, we aimed to assess the effect of periodontal therapy on some CVD risk factors including Total Cholesterol (TC), Low-Density Lipoprotein(LDL), High-Density Lipoprotein(HDL), Triglycerides(TG) and C-Reactive Protein (CRP). Fasting Blood Sugar (FBS) level has also been measured.Methods:Thirty patients (12 male and 18 female) who had severe periodontitis were tested for different blood parameters; namely Total Cholesterol (TC), Low-Density Lipoprotein (LDL), High-Density Lipoprotein(HDL), Triglycerides (TGs), C-Reactive Protein (CRP) and Fasting Blood Sugar (FBS). Enzymatic colorimetric methods were applied to measure all the parameters’ values except for CRP. The first stage of periodontal treatment comprised oral hygiene instruction as well as scaling and root planing. After 1 month, at the next stage, open flap debridement surgery was performed on all 4 quadrants of the mouth. The blood parameters were reassessed and compared with the baseline values after 3 months. Two patients (female) failed to participate in the follow-ups. The Pearson's and Spearman's correlation coefficients were calculated to determine whether changes in laboratory variables are associated with age and average probing depth or not.Results:All the assessed parameters related to 28 patients showed mean reduction which proved to be significant for CRP (p=0.011) and cholesterol (p=0.035). Among all parameters, only CRP level was found to have a significant positive correlation with pocket depth. Other blood parameters' relationship with age and probing depth proved to be insignificant.Conclusion:Considering the results, periodontal treatment may significantly lower lipid profile serum levels and some inflammatory factors.
Collapse
|
|
39
|
Schwartz SM, Virmani R, Majesky MW. An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque? F1000Res 2018; 7:F1000 Faculty Rev-1969. [PMID: 30613386 PMCID: PMC6305222 DOI: 10.12688/f1000research.15994.1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/06/2018] [Indexed: 12/13/2022] Open
Abstract
Almost 50 years ago, Earl Benditt and his son John described the clonality of the atherosclerotic plaque. This led Benditt to propose that the atherosclerotic lesion was a smooth muscle neoplasm, similar to the leiomyomata seen in the uterus of most women. Although the observation of clonality has been confirmed many times, interest in the idea that atherosclerosis might be a form of neoplasia waned because of the clinical success of treatments for hyperlipemia and because animal models have made great progress in understanding how lipid accumulates in the plaque and may lead to plaque rupture. Four advances have made it important to reconsider Benditt's observations. First, we now know that clonality is a property of normal tissue development. Second, this is even true in the vessel wall, where we now know that formation of clonal patches in that wall is part of the development of smooth muscle cells that make up the tunica media of arteries. Third, we know that the intima, the "soil" for development of the human atherosclerotic lesion, develops before the fatty lesions appear. Fourth, while the cells comprising this intima have been called "smooth muscle cells", we do not have a clear definition of cell type nor do we know if the initial accumulation is clonal. As a result, Benditt's hypothesis needs to be revisited in terms of changes in how we define smooth muscle cells and the quite distinct developmental origins of the cells that comprise the muscular coats of all arterial walls. Finally, since clonality of the lesions is real, the obvious questions are do these human tumors precede the development of atherosclerosis, how do the clones develop, what cell type gives rise to the clones, and in what ways do the clones provide the soil for development and natural history of atherosclerosis?
Collapse
Affiliation(s)
| | - Renu Virmani
- CV Path Institute, Gaithersberg, Maryland, 20878, USA
| | - Mark W. Majesky
- Center for Developmental Biology and Regenerative Medicine, Seattle Children's Hospital Research Institute, Seattle, WA, 98112, USA
| |
Collapse
|
|
40
|
Mesa F, Magan-Fernandez A, Castellino G, Chianetta R, Nibali L, Rizzo M. Periodontitis and mechanisms of cardiometabolic risk: Novel insights and future perspectives. Biochim Biophys Acta Mol Basis Dis 2018; 1865:476-484. [PMID: 30529255 DOI: 10.1016/j.bbadis.2018.12.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Revised: 11/21/2018] [Accepted: 12/03/2018] [Indexed: 01/08/2023]
Abstract
Periodontitis is an infectious and inflammatory disease of the tooth-supporting tissues caused by the accumulation of subgingival plaque and the action of specific periodontopathogenic bacteria. Periodontitis has been associated with cardiovascular diseases and considered a cardiovascular risk factor. Several mechanisms have been proposed to explain this association, such as the infection of atherosclerotic plaques by periodontal pathogens, the pro-atherogenic effect on the lipid profile, the systemic dissemination of pro-inflammatory mediators or the contribution to type 2 diabetes mellitus. Periodontal treatment has also been related to improvement in cardiometabolic risk variables, and oral hygiene techniques may be useful in reducing cardiometabolic risk. The aim of this review is to provide new and recent insights on the relationship between periodontitis and cardiometabolic risk, focusing on recent evidence. Comments on shared potential therapeutic targets, such as the role of glucagon-like peptide 1, are also highlighted.
Collapse
Affiliation(s)
- Francisco Mesa
- Periodontology Department, School of Dentistry, University of Granada, Granada, Spain
| | | | - Giuseppa Castellino
- Biomedical Department of Internal Medicine and Specialties, University of Palermo, Italy
| | - Roberta Chianetta
- Biomedical Department of Internal Medicine and Specialties, University of Palermo, Italy
| | - Luigi Nibali
- Centre for Oral Immunobiology & Regenerative Medicine, Centre for Oral Clinical Research, Institute of Dentistry, Bart's and the London School of Medicine and Dentistry, Queen Mary University of London (QMUL), London, UK
| | - Manfredi Rizzo
- Biomedical Department of Internal Medicine and Specialties, University of Palermo, Italy
| |
Collapse
|
|
41
|
Makkar H, Reynolds MA, Wadhawan A, Dagdag A, Merchant AT, Postolache TT. Periodontal, metabolic, and cardiovascular disease: Exploring the role of inflammation and mental health. Pteridines 2018; 29:124-163. [PMID: 30705520 PMCID: PMC6350811 DOI: 10.1515/pteridines-2018-0013] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Previous evidence connects periodontal disease, a modifiable condition affecting a majority of Americans, with metabolic and cardiovascular morbidity and mortality. This review focuses on the likely mediation of these associations by immune activation and their potential interactions with mental illness. Future longitudinal, and ideally interventional studies, should focus on reciprocal interactions and cascading effects, as well as points for effective preventative and therapeutic interventions across diagnostic domains to reduce morbidity, mortality and improve quality of life.
Collapse
Affiliation(s)
- Hina Makkar
- Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Mark A Reynolds
- Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA
| | - Abhishek Wadhawan
- Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Aline Dagdag
- Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Anwar T Merchant
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA
| | - Teodor T Postolache
- Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Veterans Integrated Service Network (VISN) 19, Military and Veteran Microbiome Consortium for Research and Education (MVM-CoRE), Denver, CO 80220, USA; Mental Illness Research, Education and Clinical Center (MIRECC), Veterans Integrated Service Network (VISN) 5, VA Capitol Health Care Network, Baltimore, MD 21201, USA,
| |
Collapse
|
|
42
|
Naiff P, Carneiro V, Guimarães MDC. Importance of Mechanical Periodontal Therapy in Patients with Diabetes Type 2 and Periodontitis. Int J Dent 2018; 2018:6924631. [PMID: 30356347 PMCID: PMC6176290 DOI: 10.1155/2018/6924631] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 08/29/2018] [Indexed: 11/17/2022] Open
Abstract
Periodontitis is an infectious and inflammatory disease of high prevalence worldwide and constitutes a significant oral health problem. It can lead to tooth loss. In addition, the local inflammatory process can cause the release of inflammatory mediators in the bloodstream and, consequently, contribute to the emergence of systemic effects as cardiovascular and diabetic complications. The purpose of this mini review is to alert health professionals about the risk that periodontitis represents for the onset or exacerbation of complications in individuals with type 2 diabetes mellitus and to emphasize that the mechanical treatment of periodontal disease and reestablishment of oral health are essential for the metabolic control of these patients. The periodontal therapy may help to reduce the risk of systemic complications in diabetes patients. Proper dental management should be suggested by health professionals, mainly from physicians to their patients, in order to improve the health conditions in these individuals.
Collapse
Affiliation(s)
- Priscilla Naiff
- Ph.D. Student, Faculty of Health Sciences, University of Brasilia, Distrito Federal, Brazil
| | - Valéria Carneiro
- Ph.D. Professor at Periodontics Division, University of Brasilia, Distrito Federal, Brazil
| | | |
Collapse
|
|
43
|
Pyysalo MJ, Pyysalo LM, Hiltunen J, Järnstedt J, Helminen M, Karhunen PJ, Pessi T. The dental infections in patients undergoing preoperative dental examination before surgical treatment of saccular intracranial aneurysm. BMC Res Notes 2018; 11:600. [PMID: 30126459 PMCID: PMC6102815 DOI: 10.1186/s13104-018-3704-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 08/10/2018] [Indexed: 01/09/2023] Open
Abstract
Objective Dental bacterial DNA and bacterial-driven inflammation markers have previously been detected in intracranial aneurysm tissue samples. This study aimed (i) to assess the possible presence of dental infectious foci, (ii) and the possible association between typical odontogenic bacteria and clinical dental findings in patients undergoing pre-operative dental examination before surgical treatment of saccular intracranial aneurysm. Ninety patients with an intracranial aneurysm were recruited to the study, and the patients’ teeth were routinely investigated. Clinical data and bacterial samples from the gingival pockets were collected from a subpopulation of 60 patients. Five typical dental pathogens and total bacteria amounts were measured from gingival samples using real-time quantitative PCR. Results The amounts of total bacterial and Fusobacterium nucleatum DNA were significantly higher in the patients with ≥ 6 mm gingival pockets than patients without them (p < 0.01 and p < 0.01, respectively). A total of 43% of patients with an aneurysm had gingival pockets of 6 mm or deeper. Dental infectious foci are fairly common in the Finnish population, with the prevalence of severe periodontitis being around 20%. The frequency of chronic dental infections, especially periodontitis seems to be higher in patients with intracranial aneurysm. Electronic supplementary material The online version of this article (10.1186/s13104-018-3704-z) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Mikko J Pyysalo
- Department of Oral and Maxillofacial Diseases, Tampere University Hospital, P O Box 2000, 33521, Tampere, Finland. .,Oral Health Services, City of Tampere, Tampere, Finland.
| | - Liisa M Pyysalo
- Department of Neurosurgery, Tampere University Hospital, Tampere, Finland
| | - Jenni Hiltunen
- Faculty of Medicine and Life Sciences, University of Tampere and Fimlab Laboratories Ltd, Pirkanmaa Hospital District, Tampere, Finland
| | - Jorma Järnstedt
- Medical Imaging Centre, Department of Radiology, Tampere University Hospital, Tampere, Finland
| | - Mika Helminen
- Science Centre, Pirkanmaa Hospital District, Tampere, Finland.,School of Health Sciences, University of Tampere, Tampere, Finland
| | - Pekka J Karhunen
- Faculty of Medicine and Life Sciences, University of Tampere and Fimlab Laboratories Ltd, Pirkanmaa Hospital District, Tampere, Finland.,Department of Clinical Pathology and Forensic Medicine, University of Kuopio, Kuopio, Finland
| | - Tanja Pessi
- Faculty of Medicine and Life Sciences, University of Tampere and Fimlab Laboratories Ltd, Pirkanmaa Hospital District, Tampere, Finland.,Science Centre, Pirkanmaa Hospital District, Tampere, Finland.,School of Health Sciences, University of Tampere, Tampere, Finland
| |
Collapse
|
|
44
|
Jockel-Schneider Y, Kobsar A, Stellzig-Eisenhauer A, Vogel U, Störk S, Frantz S, Schlagenhauf U, Eigenthaler M. Wild-type isolates ofPorphyromonas gingivalisderived from periodontitis patients display major variability in platelet activation. J Clin Periodontol 2018; 45:693-700. [DOI: 10.1111/jcpe.12895] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2018] [Indexed: 01/15/2023]
Affiliation(s)
| | - Anne Kobsar
- Institute of Clinical Transfusion Medicine and Hemotherapy; University Hospital Würzburg; Würzburg Germany
| | | | - Ulrich Vogel
- Institute for Hygiene and Microbiology; University of Würzburg; Würzburg Germany
| | - Stefan Störk
- Comprehensive Heart Failure Center Würzburg; Department of Internal Medicine I; University Hospital and University of Würzburg; Würzburg Germany
| | - Stefan Frantz
- Department of Internal Medicine I; University Hospital Würzburg; Würzburg Germany
| | | | - Martin Eigenthaler
- Divison of Periodontology; University Hospital Würzburg; Würzburg Germany
- Department of Orthodontics; University Hospital of Julius-Maximilians-University; Würzburg Germany
| |
Collapse
|
|
45
|
Novel Two-Component System of Streptococcus sanguinis Affecting Functions Associated with Viability in Saliva and Biofilm Formation. Infect Immun 2018; 86:IAI.00942-17. [PMID: 29339459 DOI: 10.1128/iai.00942-17] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Accepted: 01/08/2018] [Indexed: 02/07/2023] Open
Abstract
Streptococcus sanguinis is a pioneer species of teeth and a common opportunistic pathogen of infective endocarditis. In this study, we identified a two-component system, S. sanguinis SptRS (SptRS Ss ), affecting S. sanguinis survival in saliva and biofilm formation. Isogenic mutants of sptRSs (SKsptR) and sptSSs (SKsptS) showed reduced cell counts in ex vivo assays of viability in saliva compared to those of parent strain SK36 and complemented mutants. Reduced counts of the mutants in saliva were associated with reduced growth rates in nutrient-poor medium (RPMI) and increased susceptibility to the deposition of C3b and the membrane attach complex (MAC) of the complement system, a defense component of saliva and serum. Conversely, sptRSs and sptSSs mutants showed increased biofilm formation associated with higher levels of production of H2O2 and extracellular DNA. Reverse transcription-quantitative PCR (RT-qPCR) comparisons of strains indicated a global role of SptRS Ss in repressing genes for H2O2 production (2.5- to 15-fold upregulation of spxB, spxR, vicR, tpk, and ackA in sptRSs and sptSSs mutants), biofilm formation, and/or evasion of host immunity (2.1- to 11.4-fold upregulation of srtA, pcsB, cwdP, iga, and nt5e). Compatible with the homology of SptR Ss with AraC-type regulators, duplicate to multiple conserved repeats were identified in 1,000-bp regulatory regions of downstream genes, suggesting that SptR Ss regulates transcription by DNA looping. Significant transcriptional changes in the regulatory genes vicR, spxR, comE, comX, and mecA in the sptRSs and sptSSs mutants further indicated that SptRS Ss is part of a regulatory network that coordinates cell wall homeostasis, H2O2 production, and competence. This study reveals that SptRS Ss is involved in the regulation of crucial functions for S. sanguinis persistence in the oral cavity.
Collapse
|
|
46
|
Saadeh YS, Savastano LE, Gendreau JL, Pandey AS. Infected symptomatic carotid artery atheroma concurrent with bacterial endocarditis. BMJ Case Rep 2018; 2018:bcr-2017-223604. [PMID: 29545437 DOI: 10.1136/bcr-2017-223604] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Optimal management of patients with stroke due to symptomatic carotid artery disease coexistent with bacterial endocarditis is still not well established. We report the case of a patient who presented with multifocal left middle cerebral artery stroke in the setting of Enterococcus faecalis endocarditis and was found to have near-occlusive ipsilateral carotid artery stenosis in stroke workup. Carotid artery endarterectomy was performed, and atheroma material demonstrated complicated plaque with cultures positive for E. faecalis This report demonstrates that patients with cardioembolic disorders such as bacterial endocarditis with vegetations who present with stroke may benefit from evaluation for extracranial vessel stenosis. Also, additional consideration should be given to the possibility of infected atheroma in patients with symptomatic carotid stenosis with recent or active endocarditis or bacteraemia.
Collapse
Affiliation(s)
- Yamaan S Saadeh
- Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Luis E Savastano
- Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Aditya S Pandey
- Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA
| |
Collapse
|
|
47
|
Zhang Y, Wang X, Li H, Ni C, Du Z, Yan F. Human oral microbiota and its modulation for oral health. Biomed Pharmacother 2018; 99:883-893. [PMID: 29710488 DOI: 10.1016/j.biopha.2018.01.146] [Citation(s) in RCA: 300] [Impact Index Per Article: 42.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2017] [Revised: 01/04/2018] [Accepted: 01/29/2018] [Indexed: 02/07/2023] Open
Abstract
The oral microbiome is an important part of the human microbiome. The oral cavity contains several significantly different niches with distinct microbial communities. A wide range of microorganisms inhabit the human oral cavity, including bacteria, fungi, viruses, archaea and protozoa. These microorganisms form a complex ecological community that influences oral and systemic health. The most prevalent oral diseases, dental caries and periodontal diseases, are microbiota-associated diseases. Moreover, increasing evidences have supported that many systemic diseases are associated with disturbances in the oral ecosystem, such as diabetes, cardiovascular diseases and tumors. The current control of dental plaque-related diseases is nonspecific and is centered on the removal of plaque by mechanical means. Due to this realization about the oral microbiome, several new methods based on the modulation of the microbiome that aim at maintaining and reestablishing a healthy oral ecosystem have been developed.
Collapse
Affiliation(s)
- Yangheng Zhang
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Xiang Wang
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Houxuan Li
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Can Ni
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Zhibin Du
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Brisbane, Queensland, Australia.
| | - Fuhua Yan
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
| |
Collapse
|
|
48
|
Park SB, An SY, Han WJ, Park JT. Three-dimensional measurement of periodontal surface area for quantifying inflammatory burden. J Periodontal Implant Sci 2017; 47:154-164. [PMID: 28680711 PMCID: PMC5494310 DOI: 10.5051/jpis.2017.47.3.154] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 05/30/2017] [Indexed: 11/24/2022] Open
Abstract
Purpose Measurement of the root surface area (RSA) is important in periodontal treatment and for the evaluation of periodontal disease as a risk factor for systemic disease. The aim of this study was to measure the RSA at 6 mm below the cementoenamel junction (CEJ) using the Mimics software (Materialise, Leuven, Belgium). Methods We obtained cone-beam computed tomography (CBCT) data from 33 patients who had visited the Department of Oral and Maxillofacial Radiology of Dankook University Dental Hospital. The patients comprised 17 men and 16 women aged from 20 to 35 years, with a mean age of 24.4 years. Only morphologically intact teeth were included in our data. Because the third molars of the maxilla and mandible have a high deformation rate and were absent in some participants, they were not included in our research material. Results The CBCT data were reconstructed into 3-dimensional (3D) teeth models using the Mimics software, and the RSA at 6 mm below the CEJ was separated and measured using 3-Matic (Materialise). In total, 924 3D teeth models were created, and the area at 6 mm below the CEJ could be isolated in all the models. The area at 6 mm below the CEJ was measured in all teeth from the 33 patients and compared based on sex and position (maxilla vs. mandible). Conclusions In this study, we demonstrated that it was feasible to generate 3D data and to evaluate RSA values using CBCT and the Mimics software. These results provide deeper insights into the relationship between periodontal inflammatory burden and systemic diseases.
Collapse
Affiliation(s)
- Sa-Beom Park
- Department of Oral Anatomy, Dankook University College of Dentistry, Cheonan, Korea
| | - So-Youn An
- Department of Pediatric Dentistry, Wonkwang University, Daejeon, Korea
| | - Won-Jeong Han
- Department of Dentomaxillofacial Radiology, Dankook University College of Dentistry, Cheonan, Korea
| | - Jong-Tae Park
- Department of Oral Anatomy, Dankook University College of Dentistry, Cheonan, Korea
| |
Collapse
|
|
49
|
Ellis JE, Heuser R, Missan DS, Martinez D, Heningburg A, Shabilla M, Schwartz R, Fry S. Evidence for polymicrobial communities in explanted vascular filters and atheroma debris. Mol Cell Probes 2017; 33:65-77. [PMID: 28411089 DOI: 10.1016/j.mcp.2017.04.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Revised: 03/07/2017] [Accepted: 04/06/2017] [Indexed: 10/19/2022]
Abstract
RATIONALE Microbial communities have been implicated in a variety of disease processes and have been intermittently observed in arterial disease; however, no comprehensive unbiased community analysis has been performed. We hypothesize that complex microbial communities may be involved in chronic vascular diseases as well and may be effectively characterized by molecular assays. OBJECTIVE The main objective is to survey vascular debris, atheroma, and vascular filters for polymicrobial communities consisting of prokaryotic and eukaryotic microbes, specifically eukaryotic microbes. METHODS AND RESULTS We examined vascular aspirates of atheromatous debris or embolic protection filters in addition to matched peripheral blood samples, from fifteen patients, as well as three cadaveric coronary arteries from two separate patients, for microbial communities. General fluorescence microscopy by Höechst and ethidium bromide DNA stains, prokaryotic and eukaryotic community analysis by Next Generation DNA Sequencing (NGS), and a eukaryotic microbial 9 probe multiplexed quantitative PCR were used to detect and characterize the presence of putative polymicrobial communities. No prokaryotes were detected in peripheral blood; however, in 4 of 9 sequenced filters and in 2 of 7 sequenced atheroma debris samples, prokaryotic populations were identified. By DNA sequencing, eukaryotic microbes were detected in 4 of 15 blood samples, 5 of the 9 sequenced filters, and 3 of the 7 atheroma debris samples. The quantitative multiplex PCR detected sequences consistent with eukaryotic microbes in all 9 analyzed filter samples as well as 5 of the 7 atheroma debris samples. Microscopy reveals putative polymicrobial communities within filters and atheroma debris. The main contributing prokaryotic species in atheroma debris suggest a diverse and novel composition. Additionally, Funneliformis mosseae, an arbuscular mycorrhizal fungus in the Glomeraceae family, was detected in the coronary hard plaque from two patients. Well studied biofilm forming bacteria were not detectable in circulating peripheral blood and were not universally present in atheroma or filters. Analyses of the sequenced eukaryotes are consistent with a diverse of array poorly studied environmental eukaryotes. In summary, out of 15 patients, 6 exhibited molecular evidence of prokaryotes and 14 had molecular evidence of eukaryotic and/or polymicrobial communities in vivo, while 2 post-mortem coronary plaque samples displayed evidence of fungi. CONCLUSION Prokaryotes are not consistently observed in atheroma debris or filter samples; however, detection of protozoa and fungi in these samples suggests that they may play a role in arterial vascular disease or atheroma formation.
Collapse
Affiliation(s)
| | - Richard Heuser
- St. Luke's Phoenix Heart Center, Phoenix, AZ 85006, USA; University of Arizona, College of Medicine, Phoenix, AZ 85006, USA
| | | | | | | | | | | | - Stephen Fry
- Fry Laboratories, LLC, Scottsdale, AZ 85260, USA.
| |
Collapse
|
|
50
|
Palm E, Demirel I, Bengtsson T, Khalaf H. The role of toll-like and protease-activated receptors and associated intracellular signaling in Porphyromonas gingivalis-infected gingival fibroblasts. APMIS 2017; 125:157-169. [PMID: 28120492 DOI: 10.1111/apm.12645] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 11/04/2016] [Indexed: 11/28/2022]
Abstract
Porphyromonas gingivalis, which is considered a keystone agent in periodontitis, has evolved elaborate mechanisms to grow and survive in a hostile milieu. The gingival fibroblast is the major cell type in the gingiva and is considered to be important in the periodontitis-associated inflammation. As a part of the innate immune response, they produce cytokines such as CXCL8 and interleukin (IL)-6 which are believed to contribute to the destruction of the tooth-supporting tissues. This study investigates how the expression of protease-activated receptors (PAR1, PAR2) and toll-like receptors (TLR2, TLR4) changes with P. gingivalis exposure and how silencing of one receptor affects the expression of the other receptors. The importance of protein kinase C (PKC) and p38 in the regulation of CXCL8 and IL-6 was also examined. Receptors were knockdown with small-interfering RNA. PKC or p38 was blocked prior to stimulation with P. gingivalis. Fibroblasts were able to compensate for PAR1 knockdown with increased expression of PAR2. PKC and p38 were involved in the regulation of P. gingivalis-induced CXCL8 and IL-6. Our results indicate that PAR1 and PAR2 could be implicated in periodontitis and that PKC and P38 play a role in the inflammatory response in P. gingivalis-infected gingival fibroblasts.
Collapse
Affiliation(s)
- Eleonor Palm
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Isak Demirel
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Torbjörn Bengtsson
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Hazem Khalaf
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| |
Collapse
|