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Pădureanu V, Dop D, Caragea DC, Rădulescu D, Pădureanu R, Forțofoiu MC. Cardiovascular and Neurological Diseases and Association with Helicobacter Pylori Infection-An Overview. Diagnostics (Basel) 2024; 14:1781. [PMID: 39202269 PMCID: PMC11353373 DOI: 10.3390/diagnostics14161781] [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: 07/12/2024] [Revised: 08/05/2024] [Accepted: 08/14/2024] [Indexed: 09/03/2024] Open
Abstract
This article investigates the link between Helicobacter pylori (H. pylori) infection and cardiovascular and neurological disorders. Recent research suggests that H. pylori may play a role in cardiovascular diseases like atherosclerosis, myocardial infarction, and stroke, as well as neurological diseases including Alzheimer's disease, multiple sclerosis, and Parkinson's disease. Cardiovascular Diseases: H. pylori induces endothelial dysfunction and chronic inflammation, promoting atherosclerotic plaque formation and other cardiac complications. High infection prevalence in cardiovascular patients implies that systemic inflammation from H. pylori accelerates disease progression. Eradication therapies combined with anti-inflammatory and lipid-lowering treatments may reduce cardiovascular risk. Neurological Diseases: H. pylori may contribute to Alzheimer's, multiple sclerosis, and Parkinson's through systemic inflammation, neuroinflammation, and autoimmune responses. Increased infection prevalence in these patients suggests bacterial involvement in disease pathogenesis. The eradication of H. pylori could reduce neuroinflammation and improve outcomes. Discussions and Future Research: Managing H. pylori infection in clinical practice could impact public health and treatment approaches. Further research is needed to clarify these relationships. Longitudinal and mechanistic studies are essential to fully understand H. pylori's role in these conditions. Conclusions: H. pylori infection is a potential risk factor for various cardiovascular and neurological conditions. Additional research is critical for developing effective prevention and treatment strategies. Targeted therapies, including H. pylori eradication combined with anti-inflammatory treatments, could improve clinical outcomes. These findings highlight the need for an integrated clinical approach to include H. pylori evaluation and treatment.
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Affiliation(s)
- Vlad Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania; (V.P.); (M.-C.F.)
| | - Dalia Dop
- Department of Pediatrics, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Daniel Cosmin Caragea
- Department of Nephrology, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Dumitru Rădulescu
- Department of Surgery, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
| | - Rodica Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania; (V.P.); (M.-C.F.)
| | - Mircea-Cătălin Forțofoiu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania; (V.P.); (M.-C.F.)
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Aggarwal K, Singh S, Singla A, Kanagala SG, Anamika F, Singh B, Aggarwal P, Jain R. Unveiling the Silent Intruder: H. pylori's Hidden Link to Ischemic Heart Disease. Cardiol Rev 2024:00045415-990000000-00227. [PMID: 38445894 DOI: 10.1097/crd.0000000000000686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/07/2024]
Abstract
Cardiovascular disease is the leading cause of death. In addition to the well-known risk factors associated with cardiovascular disease, such as age, diabetes mellitus, smoking, hypertension, and obesity, there has been a growing concern regarding cardiac complications stemming from the Gram-negative bacteria Helicobacter pylori. While H. pylori is most commonly associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric lymphoma, it has also been implicated in extra gastric manifestations, encompassing cardiac, neurologic, ocular, and dermatologic issues. Key virulent factors for coronary artery disease include the vacuolating cytotoxin gene A and the cytotoxin-associated gene A. The most likely pathogenic mechanism of the relationship between H. pylori and coronary artery disease is initiating a chronic inflammatory process associated with infection and the modifications of classic risk factors. These alterations lead to the creation of prothrombotic and procoagulant environments. Here, we review the cardiac manifestations of H. pylori and the underlying pathophysiological mechanisms.
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Affiliation(s)
- Kanishk Aggarwal
- From the Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, IndiaDepartment of Internal Medicine
| | - Sandeep Singh
- Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN
| | - Ankur Singla
- From the Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, IndiaDepartment of Internal Medicine
| | | | - Fnu Anamika
- Department of Internal Medicine, University College of Medical Sciences, New Delhi, India
| | - Bhupinder Singh
- Department of Internal Medicine, Government Medical College, Amritsar, India
| | - Priyanka Aggarwal
- Department of Internal Medicine, Maharishi Markandeshwar Institute of Medical Science & Research, Mullana, Haryana, India
| | - Rohit Jain
- Department of Internal Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA
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Du L, Liu J, Jin C, Ma Y, Yin L, Man S, Li S, Li L, Ning Y, Zhang X. Association between Helicobacter pylori infection and carotid atherosclerosis in Chinese adults. ATHEROSCLEROSIS PLUS 2021; 44:25-30. [PMID: 36644666 PMCID: PMC9833265 DOI: 10.1016/j.athplu.2021.08.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 07/26/2021] [Accepted: 08/12/2021] [Indexed: 01/18/2023]
Abstract
Background and aims The role of Helicobacter pylori (H. pylori) infection in carotid atherosclerosis remains inconsistent and sometimes controversial. We aimed to determine whether H. pylori infection is associated with carotid atherosclerotic plaques in a large number of Chinese adults. Methods We recruited 108,210 Chinese adults who participated in a standard medical screening with both carotid ultrasonic examination and 13C-urea breath test for H.pylori infection from two Chinese cohorts. A total of 93,915 adults were included in the analysis after excluding participants with cardiovascular disease (CVD) and carotid plaques at baseline. Hazard ratio (HR) for developing carotid plaques by H. pylori infection was analyzed using the Cox proportional hazard model, with sociodemographic and clinical factors adjusted. Findings across cohorts were pooled by meta-analyses. Results 11,208 (13.13%) participants occurred carotid plaques at a median follow-up of 20 months in the MN cohort, while 1279 (14.95%) participants occurred carotid plaques at a median follow-up of 24 months in the MJ cohort. Compare with participants without H. pylori infection, participants with H. pylori infection were more likely to occur carotid plaques. After adjusting for age, sex, annual personal income, body mass index, blood pressure, blood glucose, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and estimated glomerular filtration rate, the HR was 1.04 (95%CI: 1.01-1.08). After further adjusting for education level, marital status, smoking status, alcohol drinking status, physical activity, and family history of CVD, the HR changed minimally. Additional sensitivity analyses confirmed the robustness of the results. Significant interactions of age, sex, blood pressure, blood glucose, or chronic inflammation were not observed in this research. Conclusions H. pylori infection was associated with carotid plaque onset in a large number of Chinese adults without previous CVD. These data suggested that the prevention of H. pylori infection may reduce the burden of carotid atherosclerosis.
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Affiliation(s)
- Li Du
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Jianghong Liu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Cheng Jin
- Meinian Institute of Health, Beijing, China,Department of Epidemiology, Peking University School of Public Health, Beijing, China
| | - Yuan Ma
- Meinian Institute of Health, Beijing, China,Department of Epidemiology, Peking University School of Public Health, Beijing, China
| | - Linlin Yin
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Sailimai Man
- Meinian Institute of Health, Beijing, China,Department of Epidemiology, Peking University School of Public Health, Beijing, China,Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
| | - Shijun Li
- Jinzhong Meinian Healthcare Center, Shangxi, China
| | - Liming Li
- Department of Epidemiology, Peking University School of Public Health, Beijing, China,Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
| | - Yi Ning
- Meinian Institute of Health, Beijing, China,Department of Epidemiology, Peking University School of Public Health, Beijing, China,Corresponding author. Meinian Institute of Health, No. 35 Huayuan North Road, Haidian District, Beijing, 100083, China.
| | - Xinghu Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,China National Clinical Research Center for Neurological Diseases, Beijing, China,Corresponding author. Beijing Tiantan Hospital, Capital Medical University, No.119 South 4th Ring West Road, Fengtai District, Beijing 100070, China.
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Lee M, Baek H, Park JS, Kim S, Kyung C, Baik SJ, Lee BK, Kim JH, Ahn CW, Kim KR, Kang S. Current Helicobacter pylori infection is significantly associated with subclinical coronary atherosclerosis in healthy subjects: A cross-sectional study. PLoS One 2018; 13:e0193646. [PMID: 29499055 PMCID: PMC5834174 DOI: 10.1371/journal.pone.0193646] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Accepted: 02/15/2018] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori is a gastrointestinal pathogen known to be associated with cardiovascular disease (CVD). However, most analyses about the effect of H. pylori infection have been done in patients with a history of CVD but not in healthy subjects. We evaluated the association between H. pylori infection and subclinical atherosclerosis by using cardiac multidetector computed tomography (MDCT) in healthy subjects without previous CVD. From December 2007 to February 2014, 463 subjects who underwent the rapid urease test (CLO test), pulse-wave velocity (PWV) measurement, and MDCT for a self-referred health check-up were enrolled to this study. Helicobacter pylori infection was defined on the basis of CLO test positivity on endoscopic gastric biopsy. Significant coronary artery stenosis was defined as ≥50% stenosis in any of the major epicardial coronary vessel on MDCT. The CLO-positive subjects had a lower high-density lipoprotein-cholesterol (HDL-cholesterol) level compared to the CLO-negative subjects. The incidence of significant coronary stenosis was higher in the CLO-positive group (7.6% vs. 2.9%, P = 0.01). Furthermore, the number of subjects with coronary artery calcium score >0 and log{(number of segments with plaque)+1} were also significantly higher in the CLO-positive group. However, there was no statistical difference in the number of subjects with coronary artery calcium score >100, the prevalence of any plaque nor the plaque characteristics (calcified, mixed, or soft). Pulse-wave velocity (PWV) was neither associated with CLO test positivity. The CLO-positive group was 3-fold more likely to have significant coronary artery stenosis even after adjusting for confounding factors (adjusted odds ratio 2.813, 95% confidence interval 1.051–7.528, P = 0.04). In a healthy population, current H. pylori infection was associated with subclinical but significant coronary artery stenosis. The causal relationship between H. pylori infection and subclinical atherosclerosis in a “healthy” population remains to be investigated in the future.
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Affiliation(s)
- Minyoung Lee
- Division of Endocrinology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Haeri Baek
- Division of Endocrinology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, H-plus Yangji General Hospital, Seoul, Korea
| | - Jong Suk Park
- Division of Endocrinology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea
| | - Sohee Kim
- Aswell convalescent hospital, Gwangju, Korea
| | - Chanhee Kyung
- Division of Endocrinology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Rhin Hospital, Gyeonggi-do, Korea
| | - Su Jung Baik
- Healthcare Research Team, Health Promotion Center, Gangnam Severance Hospital, Seoul, Korea
| | - Byoung Kwon Lee
- Division of Cardiology, Department of Internal Medicine Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jie-Hyun Kim
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Chul Woo Ahn
- Division of Endocrinology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea
| | - Kyung Rae Kim
- Division of Endocrinology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Shinae Kang
- Division of Endocrinology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea
- * E-mail:
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Ernst D, Widera C, Baerlecken NT, Schlumberger W, Daehnrich C, Schmidt RE, Gabrysch K, Wallentin L, Witte T. Antibodies against MYC-Associated Zinc Finger Protein: An Independent Marker in Acute Coronary Syndrome? Front Immunol 2017; 8:1595. [PMID: 29209328 PMCID: PMC5702292 DOI: 10.3389/fimmu.2017.01595] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Accepted: 11/06/2017] [Indexed: 12/26/2022] Open
Abstract
Introduction Atherosclerosis is considered the pathophysiology underlying cardiovascular (CVD), cerebrovascular, and peripheral vascular diseases. Evidence supporting an autoimmune component is emerging, with imaging studies correlating MYC-associated zinc finger protein antibody (MAZ-Ab) optical density (OD) with plaque activity. This study compares MAZ-Ab OD on ELISA testing among patients presenting with acute coronary syndromes (ACSs) to healthy controls and investigates the association of MAZ-Ab to traditional CVD risk factors. Methods Patients admitted with ACSs between August 2007 and July 2011 were included. Serum samples taken at presentation were retrospectively tested for MAZ-Ab and compared with serum from healthy volunteers with no CVD risk factors. Large-scale assessment of post-ACS prognostic relevance was performed using the established PLATO cohort. Results In total 174 ACS patients and 96 controls were included. Among ACS patients, median MAZ-Ab OD was higher compared with controls (0.46 vs. 0.27; p = 0.001). Although the majority of ACS patients (116/174; 67%) had suffered from a ST-elevation myocardial infarction, no significant differences in MAZ-Ab titers were evident between ACS subtypes (p = 0.682). No associations between MAZ-Ab OD and conventional CVD risk factors were identified. Large-scale testing revealed no prognostic stratification regarding reinfarction (OR 1.04 [95% CI: 0.94–1.16]; p = 0.436). Conclusion MAZ-Ab OD was higher or all ACS phenotypes compared with controls. Given current understanding of MAZ-Ab function, these findings support an autoimmune component to CVD independent of conventional risk factors and indeed the extent of end-organ damage.
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Affiliation(s)
- Diana Ernst
- Clinic of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany
| | - Christian Widera
- Department of Cardiology, Heart Center Oldenburg, European Medical School Oldenburg-Groningen, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Niklas T Baerlecken
- Clinic of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany
| | | | | | - Reinhold E Schmidt
- Clinic of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany
| | - Katja Gabrysch
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - Lars Wallentin
- Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - Torsten Witte
- Clinic of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany
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6
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Ernst D, Weiberg D, Baerlecken NT, Schlumberger W, Daehnrich C, Schmidt RE, Bengel FM, Derlin T, Witte T. Anti-MYC-associated zinc finger protein antibodies are associated with inflammatory atherosclerotic lesions on 18 F-fluorodeoxyglucose positron emission tomography. Atherosclerosis 2017; 259:12-19. [DOI: 10.1016/j.atherosclerosis.2017.02.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2016] [Revised: 02/09/2017] [Accepted: 02/15/2017] [Indexed: 12/29/2022]
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He C, Yang Z, Lu NH. Helicobacter pylori-an infectious risk factor for atherosclerosis? J Atheroscler Thromb 2014; 21:1229-42. [PMID: 25342566 DOI: 10.5551/jat.25775] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Accumulating evidence implicates Helicobacter pylori (H. pylori) infection in the pathogenesis of certain diseases localized outside the stomach, particularly those characterized by persistent and low-grade systematic inflammation. Recently, the role of H. pylori infection in the development of atherosclerosis and its clinical complications has received attention. Atherosclerosis is a high-cost disease, and acute events resulting from this condition rank first among morbidity and mortality statistics in most industrialized countries. Atherosclerosis is a multifactorial disorder, and traditional risk factors explain only 50% of its etiology. Therefore, identifying new risk factors for atherosclerosis is necessary. Serological studies indicate that chronic H. pylori infection, especially that with more virulent strains, may predispose patients to the onset of atherosclerosis and related adverse clinical events, and PCR studies have detected H. pylori DNA in atherosclerotic plaques, although this finding remains controversial. If this association were to be confirmed, its importance to public health would be substantial, as the eradication of H. pylori is more straightforward and less costly than the long-term treatment of other risk factors. This review investigates the potential relationship between H. pylori infection and atherosclerosis from both epidemiological and pathogenic perspectives and characterizes the potential mechanisms underlying this correlation.
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Affiliation(s)
- Cong He
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University
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8
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Abstract
Atherosclerosis is the leading global cause of mortality, morbidity, and disability. Heat shock proteins (HSPs) are a highly conserved family of proteins with diverse functions expressed by all cells exposed to environmental stress. Studies have reported that several HSPs may be potential risk markers of atherosclerosis and related cardiovascular diseases, or may be directly involved in the atherogenic process itself. HSPs are expressed by cells in atherosclerotic plaque and anti-HSP has been reported to be increased in patients with vascular disease. Autoimmune responses may be generated against antigens present within the atherosclerotic plaque, including HSP and may lead to a cycle of ongoing vascular injury. It has been suggested that by inducing a state of tolerance to these antigens, the atherogenic process may be limited and thus provide a potential therapeutic approach. It has been suggested that anti-HSPs are independent predictors of risk of vascular disease. In this review, we summarize the current understanding of HSP in cardiovascular disease and highlight their potential role as diagnostic agents and therapeutic targets.
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Sessa R, Pietro MD, Filardo S, Turriziani O. Infectious burden and atherosclerosis: A clinical issue. World J Clin Cases 2014; 2:240-249. [PMID: 25032197 PMCID: PMC4097149 DOI: 10.12998/wjcc.v2.i7.240] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 05/16/2014] [Accepted: 06/11/2014] [Indexed: 02/05/2023] Open
Abstract
Atherosclerotic cardiovascular diseases, chronic inflammatory diseases of multifactorial etiology, are the leading cause of death worldwide. In the last decade, more infectious agents, labeled as “infectious burden”, rather than any single pathogen, have been showed to contribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae (C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet aggregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule production. Others, such as Helicobacter pylori (H. pylori), influenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall (e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents (such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may contribute to atherosclerosis, defining the interplay of more infectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be amplified. Clearly, continued research and a greater awareness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis.
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Kizildag A, Arabaci T, Dogan GE. Relationship between periodontitis and cardiovascular diseases: A literature review. World J Stomatol 2014; 3:1-9. [DOI: 10.5321/wjs.v3.i1.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2013] [Revised: 08/14/2013] [Accepted: 11/16/2013] [Indexed: 02/06/2023] Open
Abstract
Periodontitis and cardiovascular disease have a complex etiology and genetics and share some common risk factors (i.e., smoking, age, diabetes, etc.). In recent years, the relationship between periodontal disease and cardiovascular disease has been investigated extensively. This research mostly focused on the fact that periodontitis is an independent risk factor for cardiovascular disease. Our aim in this article is to investigate the etiological relationship between periodontal disease and cardiovascular disease and the mechanisms involved in this association. According to the current literature, it is concluded that there is a strong relationship between these chronic disorders.
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Jaiswal V, Chauhan RS, Rout C. Common antigens prediction in bacterial bioweapons: a perspective for vaccine design. INFECTION GENETICS AND EVOLUTION 2013; 21:315-9. [PMID: 24300889 DOI: 10.1016/j.meegid.2013.11.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2013] [Revised: 11/10/2013] [Accepted: 11/11/2013] [Indexed: 01/22/2023]
Abstract
Bioweapons (BWs) are a serious threat to mankind and the lack of efficient vaccines against bacterial bioweapons (BBWs) further worsens the situation in face of BW attack. Experts believe that difficulties in detection and ease in dissemination of deadly pathogens make BW a better option for attack compared to nuclear weapons. Molecular biology techniques facilitate the use of genetically modified BBWs thus creating uncertainty on which bacteria will be used for BW attack. In the present work, available resources such as proteomic sequences of BBWs, protective antigenic proteins (PAPs) reported in Protegen database and VaxiJen dataset, and immunogenic epitopes in immune epitope database (IEDB) were used to predict potential broad-specific vaccine candidates against BBWs. Comparison of proteomes sequences of BBWs and their analyses using in-house PERL scripts identified 44 conserved proteins and many of them were known to be immunogenic. Comparison of conserved proteins against PAPs identified six either as PAPs or their homologues with a potential of providing protection against multiple pathogens. Similarly, mapping of conserved proteins against experimentally known IEDB epitopes identified six epitopes which had exact epitope match in four proteins including three from earlier predicted six PAPs. These epitopes were also reported to provide protection against several pathogens. In the backdrop of conserved heat shock GroEL protein from Salmonella enterica providing protection against five diverse bacterial pathogens involved in different diseases, and synthetic proteins produced by combination of epitopes from Mycobacterium tuberculosis and 4 viruses providing protection against both bacterium and viruses, the identified putative immunogenic conserved proteins and immune-protective epitopes can further be explored for their potential as broad-specific vaccine candidates against BBWs.
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Affiliation(s)
- Varun Jaiswal
- Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh 173234, India.
| | - Rajinder S Chauhan
- Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh 173234, India.
| | - Chittaranjan Rout
- Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh 173234, India.
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Cappello F, Marino Gammazza A, Palumbo Piccionello A, Campanella C, Pace A, Conway de Macario E, Macario AJL. Hsp60 chaperonopathies and chaperonotherapy: targets and agents. Expert Opin Ther Targets 2013; 18:185-208. [PMID: 24286280 DOI: 10.1517/14728222.2014.856417] [Citation(s) in RCA: 103] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Hsp60 (Cpn60) assembles into a tetradecamer that interacts with the co-chaperonin Hsp10 (Cpn10) to assist client polypeptides to fold, but it also has other roles, including participation in pathogenic mechanisms. AREA COVERED Hsp60 chaperonopathies are pathological conditions, inherited or acquired, in which the chaperone plays a determinant etiologic-pathogenic role. These diseases justify selection of Hsp60 as a target for developing agents that interfere with its pathogenic effects. We provide information on how to proceed. EXPERT OPINION The information available encourages the development of ways to improve Hsp60 activity (positive chaperonotherapy) when deficient or to block it (negative chaperonotherapy) when pathogenic. Many questions are still unanswered and obstacles are obvious. More information is needed to establish when and why autologous Hsp60 becomes a pathogenic autoantigen, or induces cytokine formation and inflammation, or favors carcinogenesis. Clarification of these points will take considerable time. However, analysis of the Hsp60 molecule and a search for active compounds aimed at structural sites that will affect its functioning should continue without interruption. No doubt that some of these compounds will offer therapeutic hopes and will also be instrumental for dissecting structure-function relationships at the biochemical and biological (using animal models and cultured cells) levels.
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Affiliation(s)
- Francesco Cappello
- Euro-Mediterranean Institute of Science and Technology (IEMEST) , Palermo , Italy
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13
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Matsuura E, Lopez LR, Shoenfeld Y, Ames PR. β2-glycoprotein I and oxidative inflammation in early atherogenesis: A progression from innate to adaptive immunity? Autoimmun Rev 2012; 12:241-9. [DOI: 10.1016/j.autrev.2012.04.003] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2012] [Accepted: 04/20/2012] [Indexed: 01/24/2023]
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Almanzar G, Öllinger R, Leuenberger J, Onestingel E, Rantner B, Zehm S, Cardini B, van der Zee R, Grundtman C, Wick G. Autoreactive HSP60 epitope-specific T-cells in early human atherosclerotic lesions. J Autoimmun 2012; 39:441-50. [PMID: 22901435 PMCID: PMC3516706 DOI: 10.1016/j.jaut.2012.07.006] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2012] [Revised: 07/17/2012] [Accepted: 07/19/2012] [Indexed: 01/29/2023]
Abstract
Atherosclerosis is a multifactorial chronic inflammatory disease characterized by the presence of T-cells, macrophages, and dendritic cells in the arterial intima. Classical risk factors lead to over-expression of stress proteins, especially heat shock protein 60 (HSP60). HSP60 on the surface of arterial endothelial cells (ECs) then becomes a target for pre-existing adaptive anti-HSP60 immunity resulting in infiltration of the intima by mononuclear cells. In the present study, T-cells derived from early, clinically still inapparent human atherosclerotic lesions were analyzed phenotypically and for their reactivity against HSP60 and HSP60-derived peptides. HSP60 was detected in ECs and CD40- and HLA Class II-positive cells within the intima. Effector memory CD4+ T-cells producing high amounts of interferon-γ and low levels of interleukin-4 were the dominant subpopulation. T-cells derived from late lesions displayed a more restricted T-cell receptor repertoire to HSP60-derived peptides than those isolated from early lesions. Increased levels of soluble HSP60 and circulating anti-human HSP60 autoantibodies were found in donors with late but not early lesions. This is the first functional study of T-cells derived from early human atherosclerotic lesions that supports the previously proposed concept that HSP60-reactive T-cells initiate atherosclerosis by recognition of atherogenic HSP60 epitopes.
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Affiliation(s)
- Giovanni Almanzar
- Laboratory of Autoimmunity, Section of Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Fritz-Pregl-Strasse 3, Schöpfstraße 41/1, A-6020 Innsbruck, Austria
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Leishman SJ, Ford PJ, Do HL, Palmer JE, Heng NC, West MJ, Seymour GJ, Cullinan MP. Periodontal pathogen load and increased antibody response to heat shock protein 60 in patients with cardiovascular disease. J Clin Periodontol 2012; 39:923-30. [PMID: 22882677 DOI: 10.1111/j.1600-051x.2012.01934.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2012] [Indexed: 12/23/2022]
Affiliation(s)
| | - Pauline J. Ford
- School of Dentistry; The University of Queensland; Brisbane, Australia
| | - Hong Lien Do
- School of Medicine; The University of Queensland; Brisbane, Australia
| | - Janet E. Palmer
- School of Medicine; The University of Queensland; Brisbane, Australia
| | - Nicholas C.K. Heng
- Sir John Walsh Research Institute; University of Otago; Dunedin; New Zealand
| | - Malcolm J. West
- School of Medicine; The University of Queensland; Brisbane, Australia
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16
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Liao KW, Lin CS, Chen WL, Yang CT, Lin CM, Hsu WT, Lin YY, Chiu YH, Huang KC, Wu HY, Wu MS, Wu CJ, Mao SJT, Tsai NM. Antibodies against Helicobacter pylori heat shock protein 60 aggravate HSP60-mediated proinflammatory responses. Cytokine 2011; 55:174-80. [PMID: 21565524 DOI: 10.1016/j.cyto.2011.04.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2010] [Revised: 03/29/2011] [Accepted: 04/15/2011] [Indexed: 12/23/2022]
Abstract
Anti-Helicobacter pylori heat shock protein 60 (HpHSP60) antibodies are usually found in H. pylori-infected patients and are known to be associated with the progression of gastric diseases. However, the effects of these antibodies on the functions of HpHSP60 have not been identified. This study aims to investigate the effects of the interaction between anti-HSP60 antibodies and HpHSP60 on inflammatory responses. Anti-HpHSP60 polyclonal sera and monoclonal antibodies (mAbs) were produced to evaluate their effects on HpHSP60-induced IL-8 and TNF-α activity. The results indicated that anti-HpHSP60 polyclonal sera collected from patients infected with H. pylori or from rabbit and mice immunized with HpHSP60 could significantly enhance HpHSP60-mediated IL-8 and TNF-α secretion from monocytic THP-1 cells. Similar effects were also found with anti-HpHSP60 mAbs. Further analysis revealed that this phenomenon was only carried out by anti-HpHSP60 antibody but not by other non-specific mAbs. Moreover, the non-specific mAbs decreased the synergism of HpHSP60 and anti-HpHSP60 mAbs in proinflammatory cytokine induction. Herein, we have examined the role of anti-HpHSP60 antibody in host immune responses for the first time. This study demonstrated that H. pylori HSP60/mAbs could modulate helicobacterial pathogenesis by increasing IL-8 and TNF-α production. The pathogen-specific antibodies may execute potential immune functions rather than recognize or neutralize microbes.
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Affiliation(s)
- Kuang-Wen Liao
- Department of Biological Science and Technology and Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan
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17
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Influence of CagA-positive Helicobacter pylori strains on atherosclerotic carotid disease. J Neurol 2010. [PMID: 21085982 DOI: 10.10007/s00415-010-5824-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Citotoxin-associated gene-A (CagA)-positive Helicobacter pylori strains have been associated with occurrence and destabilization of coronary atherosclerotic plaques. However, data on the relationship between CagA-positive H. pylori infection and carotid artery instability are lacking. Thus, the role of CagA antigen in patients with symptomatic and asymptomatic carotid atherosclerotic plaques was investigated. A total of 64 patients with advanced carotid artery stenosis, including 33 patients with symptomatic and 31 patients with asymptomatic internal carotid artery stenosis, verified by duplex ultrasound, all undergoing carotid endarterectomy, were studied. The control group consisted of 65 subjects without a history or presence of vascular diseases. Serology for H. pylori and CagA antigen was assessed in all participants. Specimens of atherosclerotic plaques obtained from all patients during carotid endarterectomy were analyzed immunohistochemically using anti-CagA monoclonal antibodies. The ultrasonographic plaque characteristics were also estimated. CagA antibody titers were significantly higher in symptomatic patients (8.8; range, 5.8-32.7) compared to asymptomatic patients (4.7; range, 2.1-8.8; P = 0.005) and the control group (5.0; range 2.2-7.9; P < 0.001). There was significant difference in echolucency (≥ 25% soft material) between the symptomatic and asymptomatic groups (P = 0.034) by ultrasonographic evaluation. Positive immunoreactivity between monoclonal CagA antibodies and antigens within atherosclerotic specimens was significantly higher among symptomatic patients compared to asymptomatic patients (97.0 vs. 74.2%; P = 0.009). H. pylori may play a role in the pathogenesis of the atherosclerotic process due to autoimmune mechanisms and even contribute to destabilization of carotid atherosclerotic plaques.
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18
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Rožanković PB, Huzjan AL, Čupić H, Benčić IJ, Bašić S, Demarin V. Influence of CagA-positive Helicobacter pylori strains on atherosclerotic carotid disease. J Neurol 2010; 258:753-61. [DOI: 10.1007/s00415-010-5824-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2010] [Revised: 10/20/2010] [Accepted: 10/29/2010] [Indexed: 10/18/2022]
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19
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Abstract
Atherosclerosis is an inflammatory disease, and several antigens have been shown to activate the immune response and affect the development of atherogenesis. This suggests that modulation of the immune system could represent a useful approach to prevent and/or treat this disorder. A vaccination approach might be a useful, effective tool in the modern arsenal of cardiovascular therapy and could possibly be used on a large scale at a low cost. Several modalities of vaccines have been tested against lipoproteins, cholesterol, molecules involved in cholesterol metabolism, atherosclerosis-associated microorganisms, and other molecules (heat shock protein, CD99, vascular endothelial growth factor-receptor, interleukin-2), with promising results. Nevertheless, a deeper understanding of the role of immunization in atherosclerosis will be essential to the use of vaccines in clinical medicine.
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Affiliation(s)
- Jozélio Freire de Carvalho
- Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo e Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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20
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Autoimmunity, infectious immunity, and atherosclerosis. J Clin Immunol 2010; 29:714-21. [PMID: 19795194 DOI: 10.1007/s10875-009-9333-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2009] [Accepted: 09/09/2009] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Vascular inflammation is common in certain systemic autoimmune diseases and contributes to the oxidation of low-density lipoprotein (oxLDL) and oxLDL/beta2-glycoprotein I (beta2GPI) complex formation. These complexes have been implicated as proatherogenic autoantigens that participate in the development of atherosclerotic disease. DISCUSSION We have demonstrated that the in vitro macrophage uptake of oxLDL/beta2GPI complexes increases in the presence of IgG anti-beta2GPI antibodies and that IgG immune complexes containing oxLDL/beta2GPI upregulate the expression of both scavenger and Fcgamma receptors to activate beta2GPI specific T cells. Some persistent infections may cause immune responses that promote atherogenesis. Cellular immunity (Th1) against Helicobacter pylori (H. pylori) derived heat shock protein 60 (Hp-HSP60) cross-reacts with endogenous HSP60 to cause cardiovascular disease likely by molecular mimicry. CONCLUSION Infectious cellular response may be proatherogenic,while the humoral response (antibody production) maybe protective. We review the recent progress in our understanding of autoimmunity and infectious immunity that promote atherosclerosis.
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Ayada K, Yokota K, Hirai K, Fujimoto K, Kobayashi K, Ogawa H, Hatanaka K, Hirohata S, Yoshino T, Shoenfeld Y, Matsuura E, Oguma K. Regulation of cellular immunity prevents Helicobacter pylori-induced atherosclerosis. Lupus 2010; 18:1154-68. [PMID: 19880562 DOI: 10.1177/0961203309106600] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Helicobacter pylori (H. pylori) is a predominant pathogen that causes not only gastroduodenal diseases but also extra-alimentary tract diseases. In this study, we demonstrated that H. pylori infection promoted atherogenesis in heterozygous apoe(+/ --) ldlr(+/--) mice. The male mice were fed with high fat diet from the age of 6 weeks. At the age of 16 weeks, development of atherosclerotic lesions was observed in the H. pylori-infected mice, and it seemed to be associated with an elevation of Th1-immune response against H. pylori origin-heat shock protein 60 (Hp-HSP60) and an increment of transendothelial migration of T cells. Subcutaneous immunisation with Hp-HSP60 or H. pylori eradication with antibiotics significantly reduced the progression of atherosclerosis, accompanied by a decline of Th1 differentiation and reduction of their chemotaxis beyond the endothelium. Thus, oral infection with H. pylori accelerates atherosclerosis in mice and the active immunisation with Hp-HSP60 or the eradication of H. pylori with antibiotics can moderate/prevent cellular immunity, resulting in a reduction of atherosclerosis.
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Affiliation(s)
- K Ayada
- Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
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22
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Businaro R, Profumo E, Tagliani A, Buttari B, Leone S, D’Amati G, Ippoliti F, Leopizzi M, D’Arcangelo D, Capoano R, Fumagalli L, Salvati B, Riganò R. Heat-shock protein 90: A novel autoantigen in human carotid atherosclerosis. Atherosclerosis 2009; 207:74-83. [DOI: 10.1016/j.atherosclerosis.2009.04.026] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2008] [Revised: 04/20/2009] [Accepted: 04/21/2009] [Indexed: 11/15/2022]
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23
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Ayada K, Yokota K, Kobayashi K, Shoenfeld Y, Matsuura E, Oguma K. Chronic infections and atherosclerosis. Clin Rev Allergy Immunol 2009; 37:44-8. [PMID: 18985284 DOI: 10.1007/s12016-008-8097-7] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The immune response against heat shock protein 60 (HSP60) derived from pathogens causing chronic infections is thought to be an important pro-atherogenic mechanism because high serum levels of antibodies against HSP60 have been associated with atherosclerotic diseases, such as coronary artery diseases, or cerebro-vascular events. Furthermore, the presence of HSP60-specific T lymphocytes in circulation may increase the risk of atherosclerosis. Our recent in vitro and in vivo studies have also shown an association of Helicobacter pylori-HSP60 (Hp-HSP60) specific Th1 immune responses elicited by H. pylori infection with the progression of atherosclerosis in a hyperlipidemic mouse model. These Th1 dominant immune responses may cross-react with endogenous HSP60 expressed on stressed cells of the vascular endothelium, likely due to molecular mimicry. However, the exact mechanisms by which endothelial cells display their HSP60 molecule or present HSP60 antigenic epitopes on the surface are still unclear.
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Affiliation(s)
- Kiyoshi Ayada
- Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, 700-8558, Japan
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24
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Affiliation(s)
- Eiji Matsuura
- Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan.
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25
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Cappello F, Conway de Macario E, Di Felice V, Zummo G, Macario AJL. Chlamydia trachomatis infection and anti-Hsp60 immunity: the two sides of the coin. PLoS Pathog 2009; 5:e1000552. [PMID: 19714222 PMCID: PMC2726942 DOI: 10.1371/journal.ppat.1000552] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Chlamydia trachomatis (CT) infection is one of the most common causes of reproductive tract diseases and infertility. CT-Hsp60 is synthesized during infection and is released in the bloodstream. As a consequence, immune cells will produce anti-CT-Hsp60 antibodies. Hsp60, a ubiquitous and evolutionarily conserved chaperonin, is normally sequestered inside the cell, particularly into mitochondria. However, upon cell stress, as well as during carcinogenesis, the chaperonin becomes exposed on the cell surface (sf-Hsp60) and/or is secreted from cells into the extracellular space and circulation. Reports in the literature on circulating Hsp and anti-Hsp antibodies are in many cases short on details about Hsp60 concentrations, and about the specificity spectra of the antibodies, their titers, and their true, direct, pathogenetic effects. Thus, more studies are still needed to obtain a definitive picture on these matters. Nevertheless, the information already available indicates that the concurrence of persistent CT infection and appearance of sf-Hsp60 can promote an autoimmune aggression towards stressed cells and the development of diseases such as autoimmune arthritis, multiple sclerosis, atherosclerosis, vasculitis, diabetes, and thyroiditis, among others. At the same time, immunocomplexes composed of anti-CT-Hsp60 antibodies and circulating Hsp60 (both CT and human) may form deposits in several anatomical locations, e.g., at the glomerular basal membrane. The opposite side of the coin is that pre-tumor and tumor cells with sf-Hsp60 can be destroyed with participation of the anti-Hsp60 antibody, thus stopping cancer progression before it is even noticed by the patient or physician.
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Affiliation(s)
- Francesco Cappello
- Dipartimento di Medicina Sperimentale, Sezione di Anatomia Umana Emerico Luna, Università degli Studi di Palermo, Palermo, Italy.
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26
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Abstract
Currently, the origin of autoimmune diseases is considered to be multifactorial. Genetic predisposition, immune system malfunction or even backfire, hormonal regulation, and environmental factors, i.e. infections, all play important roles in the pathogenesis of autoimmune diseases such as the antiphospholipid syndrome (APS). New drugs and strategies aimed at preventing infections could further improve the outcome of APS and other autoimmune diseases.
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27
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Campanella C, Marino Gammazza A, Mularoni L, Cappello F, Zummo G, Di Felice V. A comparative analysis of the products of GROEL-1 gene from Chlamydia trachomatis serovar D and the HSP60 var1 transcript from Homo sapiens suggests a possible autoimmune response. Int J Immunogenet 2009; 36:73-8. [PMID: 19207939 DOI: 10.1111/j.1744-313x.2008.00819.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Chlamydia trachomatis serovar D produces large quantities of HSP60-1 during infections, which accumulate inside the host cell inducing autoimmunity. We compare the aminoacid sequences of the human HSP60 with the bacterial counterpart to better elucidate how CTHSP60 may simulate HSP60 from human origin during infection and may induce an autoimmune response. As a result of the comparison we suggest several possible epitopes of the CTHSP60, which may induce autoimmunity.
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Affiliation(s)
- C Campanella
- Sezione di Anatomia Umana 'E. Luna', Dipartimento di Medicina Sperimentale, Università di Palermo, Palermo, Italy
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28
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Zinger H, Sherer Y, Shoenfeld Y. Atherosclerosis in Autoimmune Rheumatic Diseases—Mechanisms and Clinical Findings. Clin Rev Allergy Immunol 2008; 37:20-8. [PMID: 18991025 DOI: 10.1007/s12016-008-8094-x] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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29
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Selmi C, Cocchi CA, Lanfredini M, Keen CL, Gershwin ME. Chocolate at heart: The anti-inflammatory impact of cocoa flavanols. Mol Nutr Food Res 2008; 52:1340-8. [DOI: 10.1002/mnfr.200700435] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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30
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Antigen-induced immunomodulation in the pathogenesis of atherosclerosis. Clin Dev Immunol 2008; 2008:723539. [PMID: 18551190 PMCID: PMC2423423 DOI: 10.1155/2008/723539] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2007] [Revised: 04/02/2008] [Accepted: 04/30/2008] [Indexed: 12/16/2022]
Abstract
Atherosclerosis is a chronic inflammatory disorder characterised by the accumulation of monocytes/macrophages, smooth muscle cells, and lymphocytes within the arterial wall in response to the release of proinflammatory molecules. Such accumulation results in the formation of the atherosclerotic plaque, which would eventually evolve to complications such as total artery occlusion, rupture, calcification, or aneurysm. Although the molecular mechanism responsible for the development of atherosclerosis is not completely understood, it is clear that the immune system plays a key role in the development of the atherosclerotic plaque and in its complications. There are multiple antigenic stimuli that have been associated with the pathogenesis of atherosclerosis. Most of these stimuli come from modified self-molecules such as oxidised low-density lipoproteins (oxLDLs), beta2glycoprotein1 (β2GP1), lipoprotein a (LP(a)), heat shock proteins (HSPs), and protein components of the extracellular matrix such as collagen and fibrinogen in the form of advanced glycation-end (AGE) products. In addition, several foreign antigens including bacteria such as Porphyromonas gingivalis and Chlamydia pneumoniae and viruses such as enterovirus and cytomegalovirus have been associated with atherosclerosis as potentially causative or bystander participants, adding another level of complexity to the analysis of the pathophysiology of atherosclerosis. The present review summarises the most important scientific findings published within the last two decades on the importance of antigens, antigen stimulation, and adaptive immune responses in the development of atherosclerotic plaques.
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31
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Matsuura E, Kobayashi K, Lopez LR. Preventing autoimmune and infection triggered atherosclerosis for an enduring healthful lifestyle. Autoimmun Rev 2008; 7:214-22. [DOI: 10.1016/j.autrev.2007.11.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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