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Alpay Çağlar Y, Islimye Taşkin M. Association Between Chlamydia trachomatis and Helicobacter pylori with Inflammation in Polycystic Ovary Syndrome: A Cross-Sectional Study. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:2102. [PMID: 39768981 PMCID: PMC11679581 DOI: 10.3390/medicina60122102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 12/16/2024] [Accepted: 12/18/2024] [Indexed: 01/11/2025]
Abstract
Objective: Chronic low-grade inflammation occurs in polycystic ovary syndrome (PCOS), and there are many contributing factors. In this study, we aimed to investigate Helicobacter pylori and Chlamydia trachomatis infections in patients with PCOS and to evaluate the association between these microorganisms and the inflammatory process in the etiology of the disease. Materials and Methods: This comparative cross-sectional clinical study was conducted at Balıkesir University Hospital and included 40 female patients diagnosed with PCOS in the gynecology outpatients clinic and 40 healthy female controls. Demographic data were recorded. Blood hormone profiles and biochemical parameters were analyzed. An enzyme-linked immunosorbent assay test kit was used to measure H. pylori IgG and C. trachomatis IgG. Results: According to the analysis of the study data, there was no significant association between the PCOS and non-PCOS groups with regard to the presence of Helicobacter pylori IgG (p = 0.1) and Chlamydia trachomatis IgG (p = 0.338). CRP levels were significantly higher in the PCOS group (p = 0.001). In the subgroup analyses, the CRP levels were not significantly different between the H. pylori and C. trachomatis antibody-positive and -negative groups. Diabetes mellitus was significantly associated with PCOS (p = 0.005). The smoking rate was significantly higher in the control group than in the PCOS group (p = 0.036). Compared to the control group, the BMI, LH, HOMA-IR, TSH, and TG levels were significantly higher in participants with PCOS (p = 0.000; p = 0.004; p = 0.001; p = 0.001; p = 0.043; p = 0.000). FSH was lower in PCOS patients compared to controls (p = 001). In the subgroup analyses, no significant differences were found between the H. pylori and C. trachomatis antibody-positive and -negative groups. Conclusions: PCOS is characterized by chronic nonspecific low-grade inflammation. The etiopathogenesis of PCOS involves comorbidities that cause a chronic inflammatory process. However, the possible infective causes still seem to be open to investigation. In particular, studies on microbiota and periodontal diseases in PCOS may provide important contributions.
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Affiliation(s)
- Yeşim Alpay Çağlar
- Department of Infectious Disease and Clinical Microbiology, Balıkesir University School of Medicine, 10145 Balıkesir, Turkey
| | - Mine Islimye Taşkin
- Department of Obstetrics and Gynecology, Balıkesir University School of Medicine, 10145 Balıkesir, Turkey
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Ronen D, Rokach Y, Abedat S, Qadan A, Daana S, Amir O, Asleh R. Human Gut Microbiota in Cardiovascular Disease. Compr Physiol 2024; 14:5449-5490. [PMID: 39109979 DOI: 10.1002/cphy.c230012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
The gut ecosystem, termed microbiota, is composed of bacteria, archaea, viruses, protozoa, and fungi and is estimated to outnumber human cells. Microbiota can affect the host by multiple mechanisms, including the synthesis of metabolites and toxins, modulating inflammation and interaction with other organisms. Advances in understanding commensal organisms' effect on human conditions have also elucidated the importance of this community for cardiovascular disease (CVD). This effect is driven by both direct CV effects and conditions known to increase CV risk, such as obesity, diabetes mellitus (DM), hypertension, and renal and liver diseases. Cardioactive metabolites, such as trimethylamine N -oxide (TMAO), short-chain fatty acids (SCFA), lipopolysaccharides, bile acids, and uremic toxins, can affect atherosclerosis, platelet activation, and inflammation, resulting in increased CV incidence. Interestingly, this interaction is bidirectional with microbiota affected by multiple host conditions including diet, bile acid secretion, and multiple diseases affecting the gut barrier. This interdependence makes manipulating microbiota an attractive option to reduce CV risk. Indeed, evolving data suggest that the benefits observed from low red meat and Mediterranean diet consumption can be explained, at least partially, by the changes that these diets may have on the gut microbiota. In this article, we depict the current epidemiological and mechanistic understanding of the role of microbiota and CVD. Finally, we discuss the potential therapeutic approaches aimed at manipulating gut microbiota to improve CV outcomes. © 2024 American Physiological Society. Compr Physiol 14:5449-5490, 2024.
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Affiliation(s)
- Daniel Ronen
- Cardiovascular Research Center, Heart Institute, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Yair Rokach
- Cardiovascular Research Center, Heart Institute, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Suzan Abedat
- Cardiovascular Research Center, Heart Institute, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Abed Qadan
- Cardiovascular Research Center, Heart Institute, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Samar Daana
- Cardiovascular Research Center, Heart Institute, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Offer Amir
- Cardiovascular Research Center, Heart Institute, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Rabea Asleh
- Cardiovascular Research Center, Heart Institute, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
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3
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Chakaroun RM, Olsson LM, Bäckhed F. The potential of tailoring the gut microbiome to prevent and treat cardiometabolic disease. Nat Rev Cardiol 2023; 20:217-235. [PMID: 36241728 DOI: 10.1038/s41569-022-00771-0] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/05/2022] [Indexed: 12/12/2022]
Abstract
Despite milestones in preventive measures and treatment, cardiovascular disease (CVD) remains associated with a high burden of morbidity and mortality. The protracted nature of the development and progression of CVD motivates the identification of early and complementary targets that might explain and alleviate any residual risk in treated patients. The gut microbiota has emerged as a sentinel between our inner milieu and outer environment and relays a modified risk associated with these factors to the host. Accordingly, numerous mechanistic studies in animal models support a causal role of the gut microbiome in CVD via specific microbial or shared microbiota-host metabolites and have identified converging mammalian targets for these signals. Similarly, large-scale cohort studies have repeatedly reported perturbations of the gut microbial community in CVD, supporting the translational potential of targeting this ecological niche, but the move from bench to bedside has not been smooth. In this Review, we provide an overview of the current evidence on the interconnectedness of the gut microbiome and CVD against the noisy backdrop of highly prevalent confounders in advanced CVD, such as increased metabolic burden and polypharmacy. We further aim to conceptualize the molecular mechanisms at the centre of these associations and identify actionable gut microbiome-based targets, while contextualizing the current knowledge within the clinical scenario and emphasizing the limitations of the field that need to be overcome.
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Affiliation(s)
- Rima Mohsen Chakaroun
- The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany
| | - Lisa M Olsson
- The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Fredrik Bäckhed
- The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden.
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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4
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Banu Çiçek Bideci G. Chlamydias as a Zooonosis and Antibiotic Resistance in Chlamydiae. Infect Dis (Lond) 2023. [DOI: 10.5772/intechopen.110599] [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: 03/19/2023] Open
Abstract
Chlamydiosis is a disease that can be seen in different forms in the animals. In the genus Chlamydia, two species have been reported in the studies. The first is C. trachomatis, which is responsible for infections in humans and C. psittaci, which has a wide host distribution, including many animals and humans. C. psittaci is usually transmitted from poultry to humans. Along with causing flu-like conditions in humans, it has also caused abortions in pregnant women by contact with sheep and goats that have been infected and have offspring. The likelihood of pregnant women contracting the Chlamydia pathogen through contact with sheep and goats increases the zoonotic importance of the disease. There are few reports documenting antibiotic resistance in Chlamydiae. Furthermore, there are no examples of natural or permanent antibiotic resistance in strains that cause disease in humans. In some strains, the detected antibiotic resistance cannot be identified in vitro, which hinders the recognition and interpretation of antibiotic resistance.
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5
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Besir Akpinar M. A Hidden Organism, Chlamydia in the Age of Atherosclerosis. Infect Dis (Lond) 2023. [DOI: 10.5772/intechopen.109745] [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: 01/31/2023] Open
Abstract
Atherosclerosis is a chronic inflammatory disease. It is still the leading cause of mortality and morbidity in the world. Inflammation in the vessels plays the most important role in the pathogenesis of atherosclerosis. Many studies have been emphasized that Chlamydia pneumoniae triggers inflammation in the vessels and associated with atherosclerosis. It is stated that most of the chlamydial infections are asymptomatic and around 40% of adult individuals are infected. Chlamydia has different subgroups. It was thought to be a virus due to its intracellular pathogenicity, but it was included in the bacteria genus because it contains DNA and RNA chromosomes and has enzymatic activity. Chlamidya can easily be transmitted through the respiratory tract and sexual transmission. Seroepidemiological and pathological studies of atherosclerotic plaques showed the presence of Chlamydia in the plaque. This section will provide relationship between Chlamydia and atherosclerosis on the recent researces and current information will be discussed.
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Stein RA, Thompson LM. Epigenetic changes induced by pathogenic Chlamydia spp. Pathog Dis 2023; 81:ftad034. [PMID: 38031337 DOI: 10.1093/femspd/ftad034] [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: 06/15/2023] [Revised: 11/16/2023] [Accepted: 11/28/2023] [Indexed: 12/01/2023] Open
Abstract
Chlamydia trachomatis, C. pneumoniae, and C. psittaci, the three Chlamydia species known to cause human disease, have been collectively linked to several pathologies, including conjunctivitis, trachoma, respiratory disease, acute and chronic urogenital infections and their complications, and psittacosis. In vitro, animal, and human studies also established additional correlations, such as between C. pneumoniae and atherosclerosis and between C. trachomatis and ovarian cancer. As part of their survival and pathogenesis strategies as obligate intracellular bacteria, Chlamydia spp. modulate all three major types of epigenetic changes, which include deoxyribonucleic acid (DNA) methylation, histone post-translational modifications, and microRNA-mediated gene silencing. Some of these epigenetic changes may be implicated in key aspects of pathogenesis, such as the ability of the Chlamydia spp. to induce epithelial-to-mesenchymal transition, interfere with DNA damage repair, suppress cholesterol efflux from infected macrophages, act as a co-factor in human papillomavirus (HPV)-mediated cervical cancer, prevent apoptosis, and preserve the integrity of mitochondrial networks in infected host cells. A better understanding of the individual and collective contribution of epigenetic changes to pathogenesis will enhance our knowledge about the biology of Chlamydia spp. and facilitate the development of novel therapies and biomarkers. Pathogenic Chlamydia spp. contribute to epigenetically-mediated gene expression changes in host cells by multiple mechanisms.
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Affiliation(s)
- Richard A Stein
- NYU Tandon School of Engineering, Department of Chemical and Biomolecular Engineering, 6 MetroTech Center, Brooklyn, NY 11201, United States
| | - Lily M Thompson
- NYU Tandon School of Engineering, Department of Chemical and Biomolecular Engineering, 6 MetroTech Center, Brooklyn, NY 11201, United States
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7
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Hodel F, Xu ZM, Thorball CW, de La Harpe R, Letang-Mathieu P, Brenner N, Butt J, Bender N, Waterboer T, Marques-Vidal PM, Vollenweider P, Vaucher J, Fellay J. Associations of genetic and infectious risk factors with coronary heart disease. eLife 2023; 12:79742. [PMID: 36785929 PMCID: PMC9928420 DOI: 10.7554/elife.79742] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 01/22/2023] [Indexed: 02/15/2023] Open
Abstract
Coronary heart disease (CHD) is one of the most pressing health problems of our time and a major cause of preventable death. CHD results from complex interactions between genetic and environmental factors. Using multiplex serological testing for persistent or frequently recurring infections and genome-wide analysis in a prospective population study, we delineate the respective and combined influences of genetic variation, infections, and low-grade inflammation on the risk of incident CHD. Study participants are enrolled in the CoLaus|PsyCoLaus study, a longitudinal, population-based cohort with baseline assessments from 2003 through 2008 and follow-up visits every 5 years. We analyzed a subgroup of 3459 individuals with available genome-wide genotyping data and immunoglobulin G levels for 22 persistent or frequently recurring pathogens. All reported CHD events were evaluated by a panel of specialists. We identified independent associations with incident CHD using univariable and multivariable stepwise Cox proportional hazards regression analyses. Of the 3459 study participants, 210 (6.07%) had at least one CHD event during the 12 years of follow-up. Multivariable stepwise Cox regression analysis, adjusted for known cardiovascular risk factors, socioeconomic status, and statin intake, revealed that high polygenic risk (hazard ratio [HR] 1.31, 95% CI 1.10-1.56, p=2.64 × 10-3) and infection with Fusobacterium nucleatum (HR 1.63, 95% CI 1.08-2.45, p=1.99 × 10-2) were independently associated with incident CHD. In a prospective, population-based cohort, high polygenic risk and infection with F. nucleatum have a small, yet independent impact on CHD risk.
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Affiliation(s)
- Flavia Hodel
- Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de LausanneLausanneSwitzerland,Swiss Institute of BioinformaticsLausanneSwitzerland
| | - Zhi Ming Xu
- Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de LausanneLausanneSwitzerland,Swiss Institute of BioinformaticsLausanneSwitzerland
| | | | - Roxane de La Harpe
- Department of Medicine, Internal medicine, Lausanne University Hospital and University of LausanneLausanneSwitzerland
| | - Prunelle Letang-Mathieu
- Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de LausanneLausanneSwitzerland,Swiss Institute of BioinformaticsLausanneSwitzerland
| | - Nicole Brenner
- Division of Infections and Cancer Epidemiology, German Cancer Research CenterHeidelbergGermany
| | - Julia Butt
- Division of Infections and Cancer Epidemiology, German Cancer Research CenterHeidelbergGermany
| | - Noemi Bender
- Division of Infections and Cancer Epidemiology, German Cancer Research CenterHeidelbergGermany
| | - Tim Waterboer
- Division of Infections and Cancer Epidemiology, German Cancer Research CenterHeidelbergGermany
| | - Pedro Manuel Marques-Vidal
- Department of Medicine, Internal medicine, Lausanne University Hospital and University of LausanneLausanneSwitzerland
| | - Peter Vollenweider
- Department of Medicine, Internal medicine, Lausanne University Hospital and University of LausanneLausanneSwitzerland
| | - Julien Vaucher
- Precision Medicine Unit, Lausanne University Hospital and University of LausanneLausanneSwitzerland
| | - Jacques Fellay
- Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de LausanneLausanneSwitzerland,Swiss Institute of BioinformaticsLausanneSwitzerland,Precision Medicine Unit, Lausanne University Hospital and University of LausanneLausanneSwitzerland
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8
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Toll-like receptor 7 regulates cardiovascular diseases. Int Immunopharmacol 2022; 113:109390. [DOI: 10.1016/j.intimp.2022.109390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 10/20/2022] [Accepted: 10/21/2022] [Indexed: 11/05/2022]
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9
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Gonciarz W, Lechowicz Ł, Urbaniak M, Rechciński T, Chałubiński M, Broncel M, Kaca W, Chmiela M. Searching for serum biomarkers linking coronary heart disease and Helicobacter pylori infection using infrared spectroscopy and artificial neural networks. Sci Rep 2022; 12:18284. [PMID: 36316430 PMCID: PMC9622908 DOI: 10.1038/s41598-022-23191-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 10/26/2022] [Indexed: 11/07/2022] Open
Abstract
Helicobacter pylori (Hp) Gram-negative bacteria cause gastritis or gastric ulcers. They may be involved in the development of systemic diseases i.e. coronary heart disease (CHD). Both Hp infection and CHD are related to inflammation accompanied by C-reactive protein (CRP), tumor necrosis factor alfa (TNF-α) and homocysteine. Low density lipoprotein (LDL) and triglicerides are a classic risk factors of CHD. Infrared spectroscopy has been introduced for monitoring chronic infections or endogenous disorders using specific absorption bands for biocomponents typed as diagnostic markers. In this study we selected specific motives of infrared radiation (IR) spectra for the sera from CHD patients infected with Hp. In total 141 sera were used: 90 from patients with CHD, all Hp positive, and 51 from healthy donors, 32 Hp negative and 21 Hp positive. Hp status was evaluated by anti-Hp IgG antibodies and/or 13C urea breath testing. IR spectra were measured using FT-IR/FT-NIR Spectrum 400 spectrometer (PerkinElmer) chemometrically analyzed using artificial neural networks and they showed differences in absorption bands corresponding to triglicerides, CRP, homocysteine, LDL and TNF-α, and selected component groups between CHD patients infected with Hp vs healthy uninfected donors (96.15% accuracy). Triglicerides and CRP were the best biomarkers linking Hp infection with CHD.
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Affiliation(s)
- Weronika Gonciarz
- grid.10789.370000 0000 9730 2769Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland ,grid.411821.f0000 0001 2292 9126Department of Synthesis and Structural Research, Faculty of Natural Sciences, Jan Kochanowski University, Świętokrzyska 11, 25-406 Kielce, Poland
| | - Łukasz Lechowicz
- grid.411821.f0000 0001 2292 9126Departament of Microbiology, Faculty of Natural Sciences, Jan Kochanowski University, Świętokrzyska 11, 25-406 Kielce, Poland
| | - Mariusz Urbaniak
- grid.411821.f0000 0001 2292 9126Department of Synthesis and Structural Research, Faculty of Natural Sciences, Jan Kochanowski University, Świętokrzyska 11, 25-406 Kielce, Poland
| | - Tomasz Rechciński
- grid.8267.b0000 0001 2165 3025Clinic and Department of Cardiology, Medical University of Lodz, 92-213 Lodz, Poland
| | - Maciej Chałubiński
- grid.8267.b0000 0001 2165 3025Department of Immunology and Allergy, Medical University of Lodz, Pomorska 251, 91-347 Lodz, Poland
| | - Marlena Broncel
- grid.8267.b0000 0001 2165 3025Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1/5, 91-347 Lodz, Poland
| | - Wiesław Kaca
- grid.411821.f0000 0001 2292 9126Departament of Microbiology, Faculty of Natural Sciences, Jan Kochanowski University, Świętokrzyska 11, 25-406 Kielce, Poland
| | - Magdalena Chmiela
- grid.10789.370000 0000 9730 2769Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland
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Mutalub YB, Abdulwahab M, Mohammed A, Yahkub AM, AL-Mhanna SB, Yusof W, Tang SP, Rasool AHG, Mokhtar SS. Gut Microbiota Modulation as a Novel Therapeutic Strategy in Cardiometabolic Diseases. Foods 2022; 11:2575. [PMID: 36076760 PMCID: PMC9455664 DOI: 10.3390/foods11172575] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/20/2022] [Accepted: 08/22/2022] [Indexed: 11/19/2022] Open
Abstract
The human gut harbors microbial ecology that is in a symbiotic relationship with its host and has a vital function in keeping host homeostasis. Inimical alterations in the composition of gut microbiota, known as gut dysbiosis, have been associated with cardiometabolic diseases. Studies have revealed the variation in gut microbiota composition in healthy individuals as compared to the composition of those with cardiometabolic diseases. Perturbation of host-microbial interaction attenuates physiological processes and may incite several cardiometabolic disease pathways. This imbalance contributes to cardiometabolic diseases via metabolism-independent and metabolite-dependent pathways. The aim of this review was to elucidate studies that have demonstrated the complex relationship between the intestinal microbiota as well as their metabolites and the development/progression of cardiometabolic diseases. Furthermore, we systematically itemized the potential therapeutic approaches for cardiometabolic diseases that target gut microbiota and/or their metabolites by following the pathophysiological pathways of disease development. These approaches include the use of diet, prebiotics, and probiotics. With the exposition of the link between gut microbiota and cardiometabolic diseases, the human gut microbiota therefore becomes a potential therapeutic target in the development of novel cardiometabolic agents.
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Affiliation(s)
- Yahkub Babatunde Mutalub
- Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia or
- Department of Clinical Pharmacology, College of Medical Sciences, Abubakar Tafawa Balewa University, Bauchi 74027, Nigeria
| | - Monsurat Abdulwahab
- Department of Midwifery, College of Nursing Sciences, Abubakar Tafawa Balewa University Teaching Hospital, Bauchi 74027, Nigeria
| | - Alkali Mohammed
- Department of Medicine, College of Medical Sciences, Abubakar Tafawa Balewa University, Bauchi 74027, Nigeria
| | - Aishat Mutalib Yahkub
- College of Medical Sciences, Abubakar Tafawa Balewa University, Bauchi 74027, Nigeria
| | - Sameer Badri AL-Mhanna
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Wardah Yusof
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Suk Peng Tang
- Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia or
| | - Aida Hanum Ghulam Rasool
- Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia or
| | - Siti Safiah Mokhtar
- Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia or
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11
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Kim M, Huda MN, Bennett BJ. Sequence meets function-microbiota and cardiovascular disease. Cardiovasc Res 2022; 118:399-412. [PMID: 33537709 PMCID: PMC8803075 DOI: 10.1093/cvr/cvab030] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 11/20/2020] [Accepted: 01/29/2021] [Indexed: 02/07/2023] Open
Abstract
The discovery that gut-microbiota plays a profound role in human health has opened a new avenue of basic and clinical research. Application of ecological approaches where the bacterial 16S rRNA gene is queried has provided a number of candidate bacteria associated with coronary artery disease and hypertension. We examine the associations between gut microbiota and a variety of cardiovascular disease (CVD) including atherosclerosis, coronary artery disease, and blood pressure. These approaches are associative in nature and there is now increasing interest in identifying the mechanisms underlying these associations. We discuss three potential mechanisms including: gut permeability and endotoxemia, increased immune system activation, and microbial derived metabolites. In addition to discussing these potential mechanisms we highlight current studies manipulating the gut microbiota or microbial metabolites to move beyond sequence-based association studies. The goal of these mechanistic studies is to determine the mode of action by which the gut microbiota may affect disease susceptibility and severity. Importantly, the gut microbiota appears to have a significant effect on host metabolism and CVD by producing metabolites entering the host circulatory system such as short-chain fatty acids and trimethylamine N-Oxide. Therefore, the intersection of metabolomics and microbiota research may yield novel targets to reduce disease susceptibility. Finally, we discuss approaches to demonstrate causality such as specific diet changes, inhibition of microbial pathways, and fecal microbiota transplant.
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Affiliation(s)
- Myungsuk Kim
- Obesity and Metabolism Research Unit, USDA, ARS, Western Human Nutrition Research Center, Davis, CA, USA
- Department of Nutrition, University of California Davis, Davis, CA, USA
| | - Md Nazmul Huda
- Obesity and Metabolism Research Unit, USDA, ARS, Western Human Nutrition Research Center, Davis, CA, USA
- Department of Nutrition, University of California Davis, Davis, CA, USA
| | - Brian J Bennett
- Obesity and Metabolism Research Unit, USDA, ARS, Western Human Nutrition Research Center, Davis, CA, USA
- Department of Nutrition, University of California Davis, Davis, CA, USA
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12
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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.
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13
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Otani T, Nishihira K, Azuma Y, Yamashita A, Shibata Y, Asada Y, Hatakeyama K. Chlamydia pneumoniae is Prevalent in Symptomatic Coronary Atherosclerotic Plaque Samples Obtained From Directional Coronary Atherectomy, but its Quantity is Not Associated With Plaque Instability: An Immunohistochemical and Molecular Study. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2022; 15:2632010X221125179. [PMID: 36176379 PMCID: PMC9513565 DOI: 10.1177/2632010x221125179] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 08/23/2022] [Indexed: 11/16/2022]
Abstract
Aim To clarify whether there is any association between the extent of Chlamydia pneumoniae (C. pneumoniae) infection and plaque instability or post-directional coronary atherectomy (DCA) restenosis, we determined the frequency of C. pneumoniae infection and its localization in symptomatic coronary atherosclerotic plaques using specimens obtained from DCA. Methods and results Immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-PCR) revealed the existence of C. pneumoniae in all 50 specimens of coronary atherosclerotic plaques obtained by DCA. C. pneumoniae-positive cell ratio determined with IHC or copy numbers of C. pneumoniae DNA detected by RT-PCR did not differ significantly between patients with stable angina pectoris and those with acute coronary syndrome (IHC: 16.4 ± 7.6% vs 18.0 ± 7.1%, P = .42; RT-PCR: no. of cases with high copy numbers 12/25 vs 10/25, P = .78), or between patients with subsequent post-DCA restenosis and those without (IHC: 17.1 ± 8.0% vs 18.0 ± 7.4%, P = .74; RT-PCR: 5/12 vs 10/21, P = 1.00). Conclusions C. pneumoniae was highly prevalent in coronary atherosclerotic plaques of patients who underwent DCA. However, the extent of C. pneumoniae infection in coronary atherosclerotic plaques was not associated with plaque instability or post-DCA restenosis.
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Affiliation(s)
- Tomoyuki Otani
- Department of Pathology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.,Department of Pathology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Kensaku Nishihira
- Department of Cardiology, Miyazaki Medical Association Hospital, Miyazaki, Japan
| | - Yoshinao Azuma
- Molecular Biochemistry Lab, Biology-Oriented Science and Technology, Kindai University, Kinokawa, Wakayama, Japan
| | - Atsushi Yamashita
- Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Yoshisato Shibata
- Department of Cardiology, Miyazaki Medical Association Hospital, Miyazaki, Japan
| | - Yujiro Asada
- Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.,Department of Pathology, Miyazaki Medical Association Hospital, Miyazaki, Japan
| | - Kinta Hatakeyama
- Department of Pathology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.,Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
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14
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Wu X, Cheng B, Guo X, Wu Q, Sun S, He P. PPARα/γ signaling pathways are involved in Chlamydia pneumoniae-induced foam cell formation via upregulation of SR-A1 and ACAT1 and downregulation of ABCA1/G1. Microb Pathog 2021; 161:105284. [PMID: 34767930 DOI: 10.1016/j.micpath.2021.105284] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 10/10/2021] [Accepted: 11/04/2021] [Indexed: 12/12/2022]
Abstract
Chlamydia pneumoniae (Cpn) has been reported to be involved in the pathogenesis of early atherosclerosis by inducing macrophage-derived foam cell formation in the presence of low-density lipoprotein (LDL). However, the biochemical mechanisms underlying Cpn-induced foam cell formation are still not fully elucidated. The present study showed that in LDL-treated THP-1-derived macrophages, Cpn not only upregulated the expression of scavenger receptor A1 (SR-A1) and acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), but it also downregulated the expression of ATP binding cassette transporters (ABCA1 and ABCG1) at both the mRNA and protein levels. These processes facilitated cholesterol accumulation and promoted macrophage-derived foam cell formation. Treatment with the peroxisome proliferator-activated receptor (PPAR)-γ agonist rosiglitazone or the PPARα agonist fenofibrate decreased the number of foam cells induced by Cpn, while the PPARγ antagonist GW9662, the PPARα antagonist MK886, or PPARα/γ siRNAs enhanced the effect of Cpn on foam cell formation and gene expression of SR-A1, ACAT1, and ABCA1/G1. Moreover, the PPARγ agonist rosiglitazone reversed the downregulation of CD36 by Cpn, while PPARγ siRNA and the PPARγ inhibitor GW9662 further suppressed CD36 expression. However, the PPARα agonist, inhibitor, and siRNA all showed no effect on CD36 expression. In conclusion, the PPARα and PPARγ pathways are both involved in Cpn-induced macrophage-derived foam cell formation by upregulating SR-A1 and ACAT1 and downregulating ABCA1/G1 expression.
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Affiliation(s)
- Xiaohua Wu
- Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Department of Geriatrics, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, 316021, China
| | - Bei Cheng
- Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiaojuan Guo
- Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qinqin Wu
- Department of Geriatrics, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shan Sun
- Department of Geriatrics, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ping He
- Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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15
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Selvaraj J, Perumal S, Rex J, Mohan SK, Suga SSD, Rekh UV, Vishnupriya V, Vijayalakshmi P, Ponnulakshmi R. The porin AaxA protein model from Chlamydia pneumonia. Bioinformation 2021; 16:786-788. [PMID: 34675464 PMCID: PMC8503770 DOI: 10.6026/97320630016786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 08/21/2020] [Accepted: 08/23/2020] [Indexed: 11/23/2022] Open
Abstract
Chlamydophila pneumoniae is an intracellular pathogen accountable for various acute respiratory infections. C. pneumoniae has a gene cluster which encodes a putative outer membrane porin (aaxA), arginine decarboxylase (CPn1032 or aaxB) and a putative
cytoplasmic membrane transporter (CPn1031 or aaxC). Therefore, it is of interest to document a molecular protein model of porin AaxA from Chlamydia pneumonia to gain structure to functional insight on the protein.
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Affiliation(s)
- Jayaraman Selvaraj
- Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 600 077, India
| | - Srinivasan Perumal
- Department of Biochemistry, School of Life Sciences, Vels Institute of Science Technology and Advanced Studies (VISTAS), Pallavaram, Chennai- 600 117, India
| | - Josephine Rex
- Department of Biochemistry, Panimalar Medical College Hospital & Research Institute, Varadharajapuram, Poonamallee, Chennai - 600 123, India
| | - Surapaneni Krishna Mohan
- Department of Biochemistry, Panimalar Medical College Hospital & Research Institute, Varadharajapuram, Poonamallee, Chennai - 600 123, India
| | - Sumetha Suga Deiva Suga
- PG & Research Department of Biotechnology & Bioinformatics, Holy Cross College (Autonomous), Trichy- 620002, Tamil Nadu, India
| | - Umapathy Vidhya Rekh
- Central Research Laboratory, Meenakshi Academy of Higher Education and Research, Chennai-600 078, India
| | - Veeraraghavan Vishnupriya
- Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 600 077, India
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Li BW, Liu Y, Zhang L, Guo XQ, Wen C, Zhang F, Luo XY, Xia YP. Cytotoxin-associated gene A (CagA) promotes aortic endothelial inflammation and accelerates atherosclerosis through the NLRP3/caspase-1/IL-1β axis. FASEB J 2021; 35:e21942. [PMID: 34670018 DOI: 10.1096/fj.202100695rr] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/18/2021] [Accepted: 09/07/2021] [Indexed: 11/11/2022]
Abstract
Atherosclerosis is a chronic inflammatory disease. Pathophysiological similarities between chronic infections and atherosclerosis triggered interests between these conditions. The seroepidemiological study showed that Helicobacter pylori strains that express cytotoxin-associated gene A (CagA), an oncoprotein and a major virulence factor, was positively correlated with atherosclerosis and related clinical events. Nevertheless, the underlying mechanism is poorly understood. In this study, the seroprevalence of infection by H. pylori and by strains express CagA assessed by enzyme-linked immunosorbent assay (ELISA) showed that the prevalence of CagA strains rather than H. pylori in patients was positively correlated with atherogenesis. Correspondingly, we found that CagA augmented the growth of plaque of ApoE-/- mice in the early stage of atherosclerosis and promoted the expression of adhesion molecules and inflammatory cytokines in mouse aortic endothelial cells (MAECs). Mechanistically, both si-NLRP3 and si-IL-1β mitigated the promoting effect of CagA on the inflammatory activation of HAECs. In vivo, the inhibition of NLRP3 by MCC950 significantly attenuated the promoting effect of CagA on plaque growth of ApoE-/- mice. We also propose NLRP3 as a potential therapeutic target for CagA-positive H. pylori infection-related atherosclerosis and emphasize the importance of inflammation in atherosclerosis pathology.
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Affiliation(s)
- Bo-Wei Li
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Liu
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Zhang
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiao-Qing Guo
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cheng Wen
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Feng Zhang
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xue-Ying Luo
- Affiliated Wuhan Mental Health Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuan-Peng Xia
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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17
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The role of Helicobacter cinaedi in the development of atherosclerosis. POSTEP HIG MED DOSW 2021. [DOI: 10.2478/ahem-2021-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Helicobacter cinaedi (H. cinaedi) is a Gram-negative curved motile rod that causes bloodstream or enteric infections. It was suggested that H. cinaedi was involved in the progression of atherosclerosis. We aimed to investigate the presence of H. cinaedi DNA using a nested-polymerase chain reaction (PCR) in atheroma plaques from patients with atherosclerosis-induced vascular diseases. A total of 129 patients diagnosed with valvular heart disease due to atherosclerosis and 146 patients with non-atherosclerotic post-stenotic dilatation were included as the patient and the control groups, respectively. The ATCC BA847 H. cinaedi strain was used as the positive control for the nested-PCR method. We investigated H. cinaedi DNA in our study groups using the nested-PCR method and detected only six H. cinaedi DNA (4.65%) in the 129 atherosclerotic patient group. We detected significant difference between patient and control groups with respect to the presence of H. cinaedi on the basis of Fischer’s exact test (p = 0.010) by univariate analysis. Age (OR: 1.042, p = 0.016), total cholesterol (≥200 mg/dL) (OR: 1.849, p = 0.0001), and high-density lipoprotein (≥50 mg/dL) (OR: 0.745, p = 0.039) levels were detected as independent variables for the risk of atherosclerosis development in the patient group. The presence of H. cinaedi was not detected as an independent variable in a multivariate analysis. Previous studies suggested that H. cinaedi-induced oral infections might translocate to vascular tissue and induce chronic inflammation in the aorta, which subsequently may lead to atherosclerotic plaque formation. In conclusion, we could not suggest that there is a causal relationship between H. cinaedi and the development of atherosclerosis. However, age (OR: 1.042), total cholesterol (≥200 mg/dL, OR: 1.849), and high-density lipoprotein (≥50 mg/dL, OR: 0.745, as protective) levels have a significant role in the pathogenesis of atherosclerosis development. We also suggest that the presence of H. cinaedi may contribute to the risk of atherosclerosis development due to the univariate comparison result.
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18
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Sethi NJ, Safi S, Korang SK, Hróbjartsson A, Skoog M, Gluud C, Jakobsen JC. Antibiotics for secondary prevention of coronary heart disease. Cochrane Database Syst Rev 2021; 2:CD003610. [PMID: 33704780 PMCID: PMC8094925 DOI: 10.1002/14651858.cd003610.pub4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Coronary heart disease is the leading cause of mortality worldwide with approximately 7.4 million deaths each year. People with established coronary heart disease have a high risk of subsequent cardiovascular events including myocardial infarction, stroke, and cardiovascular death. Antibiotics might prevent such outcomes due to their antibacterial, antiinflammatory, and antioxidative effects. However, a randomised clinical trial and several observational studies have suggested that antibiotics may increase the risk of cardiovascular events and mortality. Furthermore, several non-Cochrane Reviews, that are now outdated, have assessed the effects of antibiotics for coronary heart disease and have shown conflicting results. No previous systematic review using Cochrane methodology has assessed the effects of antibiotics for coronary heart disease. OBJECTIVES We assessed the benefits and harms of antibiotics compared with placebo or no intervention for the secondary prevention of coronary heart disease. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-EXPANDED, and BIOSIS in December 2019 in order to identify relevant trials. Additionally, we searched TRIP, Google Scholar, and nine trial registries in December 2019. We also contacted 11 pharmaceutical companies and searched the reference lists of included trials, previous systematic reviews, and other types of reviews. SELECTION CRITERIA Randomised clinical trials assessing the effects of antibiotics versus placebo or no intervention for secondary prevention of coronary heart disease in adult participants (≥18 years). Trials were included irrespective of setting, blinding, publication status, publication year, language, and reporting of our outcomes. DATA COLLECTION AND ANALYSIS Three review authors independently extracted data. Our primary outcomes were all-cause mortality, serious adverse event according to the International Conference on Harmonization - Good Clinical Practice (ICH-GCP), and quality of life. Our secondary outcomes were cardiovascular mortality, myocardial infarction, stroke, and sudden cardiac death. Our primary time point of interest was at maximum follow-up. Additionally, we extracted outcome data at 24±6 months follow-up. We assessed the risks of systematic errors using Cochrane 'Rosk of bias' tool. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes. We calculated absolute risk reduction (ARR) or increase (ARI) and number needed to treat for an additional beneficial outcome (NNTB) or for an additional harmful outcome (NNTH) if the outcome result showed a beneficial or harmful effect, respectively. The certainty of the body of evidence was assessed by GRADE. MAIN RESULTS We included 38 trials randomising a total of 26,638 participants (mean age 61.6 years), with 23/38 trials reporting data on 26,078 participants that could be meta-analysed. Three trials were at low risk of bias and the 35 remaining trials were at high risk of bias. Trials assessing the effects of macrolides (28 trials; 22,059 participants) and quinolones (two trials; 4162 participants) contributed with the vast majority of the data. Meta-analyses at maximum follow-up showed that antibiotics versus placebo or no intervention seemed to increase the risk of all-cause mortality (RR 1.06; 95% CI 0.99 to 1.13; P = 0.07; I2 = 0%; ARI 0.48%; NNTH 208; 25,774 participants; 20 trials; high certainty of evidence), stroke (RR 1.14; 95% CI 1.00 to 1.29; P = 0.04; I2 = 0%; ARI 0.73%; NNTH 138; 14,774 participants; 9 trials; high certainty of evidence), and probably also cardiovascular mortality (RR 1.11; 95% CI 0.98 to 1.25; P = 0.11; I2= 0%; 4674 participants; 2 trials; moderate certainty of evidence). Little to no difference was observed when assessing the risk of myocardial infarction (RR 0.95; 95% CI 0.88 to 1.03; P = 0.23; I2 = 0%; 25,523 participants; 17 trials; high certainty of evidence). No evidence of a difference was observed when assessing sudden cardiac death (RR 1.08; 95% CI 0.90 to 1.31; P = 0.41; I2 = 0%; 4520 participants; 2 trials; moderate certainty of evidence). Meta-analyses at 24±6 months follow-up showed that antibiotics versus placebo or no intervention increased the risk of all-cause mortality (RR 1.25; 95% CI 1.06 to 1.48; P = 0.007; I2 = 0%; ARI 1.26%; NNTH 79 (95% CI 335 to 42); 9517 participants; 6 trials; high certainty of evidence), cardiovascular mortality (RR 1.50; 95% CI 1.17 to 1.91; P = 0.001; I2 = 0%; ARI 1.12%; NNTH 89 (95% CI 261 to 49); 9044 participants; 5 trials; high certainty of evidence), and probably also sudden cardiac death (RR 1.77; 95% CI 1.28 to 2.44; P = 0.0005; I2 = 0%; ARI 1.9%; NNTH 53 (95% CI 145 to 28); 4520 participants; 2 trials; moderate certainty of evidence). No evidence of a difference was observed when assessing the risk of myocardial infarction (RR 0.95; 95% CI 0.82 to 1.11; P = 0.53; I2 = 43%; 9457 participants; 5 trials; moderate certainty of evidence) and stroke (RR 1.17; 95% CI 0.90 to 1.52; P = 0.24; I2 = 0%; 9457 participants; 5 trials; high certainty of evidence). Meta-analyses of trials at low risk of bias differed from the overall analyses when assessing cardiovascular mortality at maximum follow-up. For all other outcomes, meta-analyses of trials at low risk of bias did not differ from the overall analyses. None of the trials specifically assessed serious adverse event according to ICH-GCP. No data were found on quality of life. AUTHORS' CONCLUSIONS Our present review indicates that antibiotics (macrolides or quinolones) for secondary prevention of coronary heart disease seem harmful when assessing the risk of all-cause mortality, cardiovascular mortality, and stroke at maximum follow-up and all-cause mortality, cardiovascular mortality, and sudden cardiac death at 24±6 months follow-up. Current evidence does, therefore, not support the clinical use of macrolides and quinolones for the secondary prevention of coronary heart disease. Future trials on the safety of macrolides or quinolones for the secondary prevention in patients with coronary heart disease do not seem ethical. In general, randomised clinical trials assessing the effects of antibiotics, especially macrolides and quinolones, need longer follow-up so that late-occurring adverse events can also be assessed.
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Affiliation(s)
- Naqash J Sethi
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Sanam Safi
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Steven Kwasi Korang
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Asbjørn Hróbjartsson
- Centre for Evidence-Based Medicine Odense (CEBMO) and Cochrane Denmark, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Open Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark
| | - Maria Skoog
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Clinical Study Support, Clinical Studies Sweden - Forum South, Lund, Sweden
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen, Denmark
- Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Janus C Jakobsen
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen, Denmark
- Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
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19
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The association of Chlamydia pneumoniae infection with atherosclerosis: Review and update of in vitro and animal studies. Microb Pathog 2021; 154:104803. [PMID: 33609645 DOI: 10.1016/j.micpath.2021.104803] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 12/24/2020] [Accepted: 02/08/2021] [Indexed: 01/08/2023]
Abstract
Previous studies have tended to relate Chlamydia pneumoniae (Cpn) infection to atherosclerosis. However, while serological studies have mostly reinforced this hypothesis, inconsistent and even contradictory findings have been reported in various researches. Recent papers have pointed to the significance of Cpn in atherosclerotic lesions, which are regarded as the initiator and cause of chronic inflammation. This bacterium develops atherosclerosis by phenotypic changes in vascular smooth muscle cells, dysregulation of endothelin-1 in the vascular wall, and releasing pro-inflammatory cytokines from Toll-like receptor-2 (TLR2). Furthermore, Cpn infection, particularly under hyperlipidemic conditions, enhances monocyte adhesion to endothelium; changes the physiology of the host, e.g., cholesterol homeostasis; and activates the Low-density lipoprotein (LDL) receptor, which is the initial step in atherogenesis. On the other hand, it has been reported that Cpn, even without the immune system of the host, has the ability to stimulate arterial thickening. Moreover, there is evidence that Cpn can increase the impact of the classical risk factors such as hyperlipidemia, pro-inflammatory cytokines, and smoking for atherosclerosis. Furthermore, animal studies have shown that Cpn infection can induce atherosclerotic, which alongside hyperlipidemia is a co-risk factor for cardiovascular disease. Although the exact link between Cpn and atherosclerosis has not been determined yet, previous studies have reported possible mechanisms of pathogenesis for this bacterium. Accordingly, investigating the exact role of this infection in causing atherosclerosis may be helpful in controlling the disease.
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20
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Abstract
Surprisingly little formal research has examined the issue of major bacterial infections in chronic dialysis patients. This is a surprising situation, because uremia is a classic state of immune hyporesponsiveness, and infection rates are believed to be several times higher in dialysis populations than in age-matched segments of the general population. The present paper focuses on the clinical epidemiology of major bacterial infections in dialysis patients, associations between bacterial infections and cardiovascular disease, and interventions aimed at averting these infections.
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Affiliation(s)
- Robert N. Foley
- Chronic Disease Research Group, Minneapolis, Minnesota and University of Minnesota, Minneapolis, Minnesota, U.S.A
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21
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Super-Resolution Fluorescence Microscopy Reveals Clustering Behaviour of Chlamydia pneumoniae's Major Outer Membrane Protein. BIOLOGY 2020; 9:biology9100344. [PMID: 33092039 PMCID: PMC7589890 DOI: 10.3390/biology9100344] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/16/2020] [Accepted: 10/16/2020] [Indexed: 12/20/2022]
Abstract
Chlamydia pneumoniae is a Gram-negative bacterium responsible for a number of human respiratory diseases and linked to some chronic inflammatory diseases. The major outer membrane protein (MOMP) of Chlamydia is a conserved immunologically dominant protein located in the outer membrane, which, together with its surface exposure and abundance, has led to MOMP being the main focus for vaccine and antimicrobial studies in recent decades. MOMP has a major role in the chlamydial outer membrane complex through the formation of intermolecular disulphide bonds, although the exact interactions formed are currently unknown. Here, it is proposed that due to the large number of cysteines available for disulphide bonding, interactions occur between cysteine-rich pockets as opposed to individual residues. Such pockets were identified using a MOMP homology model with a supporting low-resolution (~4 Å) crystal structure. The localisation of MOMP in the E. coli membrane was assessed using direct stochastic optical reconstruction microscopy (dSTORM), which showed a decrease in membrane clustering with cysteine-rich regions containing two mutations. These results indicate that disulphide bond formation was not disrupted by single mutants located in the cysteine-dense regions and was instead compensated by neighbouring cysteines within the pocket in support of this cysteine-rich pocket hypothesis.
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22
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Presence of bacterial DNA in thrombotic material of patients with myocardial infarction. Sci Rep 2020; 10:16299. [PMID: 33004892 PMCID: PMC7530676 DOI: 10.1038/s41598-020-73011-5] [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: 05/15/2020] [Accepted: 09/07/2020] [Indexed: 12/29/2022] Open
Abstract
Infectious agents have been suggested to be involved in etiopathogenesis of Acute Coronary Syndrome (ACS). However, the relationship between bacterial infection and acute myocardial infarction (AMI) has not yet been completely clarified. The objective of this study is to detect bacterial DNA in thrombotic material of patients with ACS with ST-segment elevation (STEMI) treated with Primary Percutaneous Coronary Intervention (PPCI). We studied 109 consecutive patients with STEMI, who underwent thrombus aspiration and arterial peripheral blood sampling. Testing for bacterial DNA was performed by probe-based real-time Polymerase Chain Reaction (PCR). 12 probes and primers were used for the detection of Aggregatibacter actinomycetemcomitans, Chlamydia pneumoniae, viridans group streptococci, Porphyromonas gingivalis, Fusobacterium nucleatum, Tannarella forsythia, Treponema denticola, Helycobacter pylori, Mycoplasma pneumoniae, Staphylococus aureus, Prevotella intermedia and Streptococcus mutans. Thus, DNA of four species of bacteria was detected in 10 of the 109 patients studied. The most frequent species was viridans group streptococci (6 patients, 5.5%), followed by Staphylococus aureus (2 patients, 1.8%). Moreover, a patient had DNA of Porphyromonas gingivalis (0.9%); and another patient had DNA of Prevotella intermedia (0.9%). Bacterial DNA was not detected in peripheral blood of any of our patients. In conclusion, DNA of four species of endodontic and periodontal bacteria was detected in thrombotic material of 10 STEMI patients. Bacterial DNA was not detected in the peripheral blood of patients with bacterial DNA in their thrombotic material. Bacteria could be latently present in plaques and might play a role in plaque instability and thrombus formation leading to ACS.
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23
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Abstract
Fecal microbial community changes are associated with numerous disease states, including cardiovascular disease (CVD). However, such data are merely associative. A causal contribution for gut microbiota in CVD has been further supported by a multitude of more direct experimental evidence. Indeed, gut microbiota transplantation studies, specific gut microbiota-dependent pathways, and downstream metabolites have all been shown to influence host metabolism and CVD, sometimes through specific identified host receptors. Multiple metaorganismal pathways (involving both microbe and host) both impact CVD in animal models and show striking clinical associations in human studies. For example, trimethylamine N-oxide and, more recently, phenylacetylglutamine are gut microbiota-dependent metabolites whose blood levels are associated with incident CVD risks in large-scale clinical studies. Importantly, a causal link to CVD for these and other specific gut microbial metabolites/pathways has been shown through numerous mechanistic animal model studies. Phenylacetylglutamine, for example, was recently shown to promote adverse cardiovascular phenotypes in the host via interaction with multiple ARs (adrenergic receptors)-a class of key receptors that regulate cardiovascular homeostasis. In this review, we summarize recent advances of microbiome research in CVD and related cardiometabolic phenotypes that have helped to move the field forward from associative to causative results. We focus on microbiota and metaorganismal compounds/pathways, with specific attention paid to short-chain fatty acids, secondary bile acids, trimethylamine N-oxide, and phenylacetylglutamine. We also discuss novel therapeutic strategies for directly targeting the gut microbiome to improve cardiovascular outcomes.
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Affiliation(s)
- Marco Witkowski
- From the Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute (M.W., T.L.W., S.L.H.), Cleveland Clinic, OH.,Center for Microbiome and Human Health (M.W., S.L.H.), Cleveland Clinic, OH
| | - Taylor L Weeks
- From the Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute (M.W., T.L.W., S.L.H.), Cleveland Clinic, OH.,Department of Cardiovascular Medicine, Heart and Vascular Institute (S.L.H.), Cleveland Clinic, OH
| | - Stanley L Hazen
- From the Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute (M.W., T.L.W., S.L.H.), Cleveland Clinic, OH.,Center for Microbiome and Human Health (M.W., S.L.H.), Cleveland Clinic, OH
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24
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Li B, Xia Y, Hu B. Infection and atherosclerosis: TLR-dependent pathways. Cell Mol Life Sci 2020; 77:2751-2769. [PMID: 32002588 PMCID: PMC7223178 DOI: 10.1007/s00018-020-03453-7] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 01/02/2020] [Accepted: 01/03/2020] [Indexed: 12/15/2022]
Abstract
Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, including acute coronary syndromes (ACS), myocardial infarction (MI) and stroke. In addition to a series of typical risk factors for atherosclerosis, like hyperlipidemia, hypertension, smoking and obesity, emerging evidence suggests that atherosclerosis is a chronic inflammatory disease, suggesting that chronic infection plays an important role in the development of atherosclerosis. Toll-like receptors (TLRs) are the most characteristic members of pattern recognition receptors (PRRs), which play an important role in innate immune mechanism. TLRs play different roles in different stages of infection of atherosclerosis-related pathogens such as Chlamydia pneumoniae (C. pneumoniae), periodontal pathogens including Porphyromonas gingivalis (P. gingivalis), Helicobacter pylori (H. pylori) and human immunodeficiency virus (HIV). Overall, activation of TLR2 and 4 seems to have a profound impact on infection-related atherosclerosis. This article reviews the role of TLRs in the process of atherosclerosis after C. pneumoniae and other infections and the current status of treatment, with a view to providing a new direction and potential therapeutic targets for the study of ASVD.
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Affiliation(s)
- Bowei Li
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yuanpeng Xia
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Bo Hu
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Zhou Y, Little PJ, Downey L, Afroz R, Wu Y, Ta HT, Xu S, Kamato D. The Role of Toll-like Receptors in Atherothrombotic Cardiovascular Disease. ACS Pharmacol Transl Sci 2020; 3:457-471. [PMID: 32566912 PMCID: PMC7296543 DOI: 10.1021/acsptsci.9b00100] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Indexed: 02/06/2023]
Abstract
Toll-like receptors (TLRs) are dominant components of the innate immune system. Activated by both pathogen-associated molecular patterns and damage-associated molecular patterns, TLRs underpin the pathology of numerous inflammation related diseases that include not only immune diseases, but also cardiovascular disease (CVD), diabetes, obesity, and cancers. Growing evidence has demonstrated that TLRs are involved in multiple cardiovascular pathophysiologies, such as atherosclerosis and hypertension. Specifically, a trial called the Canakinumab Anti-inflammatory Thrombosis Outcomes Study showed the use of an antibody that neutralizes interleukin-1β, reduces the recurrence of cardiovascular events, demonstrating inflammation as a therapeutic target and also the research value of targeting the TLR system in CVD. In this review, we provide an update of the interplay between TLR signaling, inflammatory mediators, and atherothrombosis, with an aim to identify new therapeutic targets for atherothrombotic CVD.
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Affiliation(s)
- Ying Zhou
- School
of Pharmacy, University of Queensland, Pharmacy
Australia Centre of Excellence, Woolloongabba, Queensland 4102, Australia
| | - Peter J. Little
- School
of Pharmacy, University of Queensland, Pharmacy
Australia Centre of Excellence, Woolloongabba, Queensland 4102, Australia
- Department
of Pharmacy, Xinhua College of Sun Yat-Sen
University, Tianhe District, Guangzhou, Guangdong Province 510520, China
| | - Liam Downey
- School
of Pharmacy, University of Queensland, Pharmacy
Australia Centre of Excellence, Woolloongabba, Queensland 4102, Australia
| | - Rizwana Afroz
- School
of Pharmacy, University of Queensland, Pharmacy
Australia Centre of Excellence, Woolloongabba, Queensland 4102, Australia
| | - Yuao Wu
- Australian
Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, St Lucia, Queensland 4072, Australia
| | - Hang T. Ta
- School
of Pharmacy, University of Queensland, Pharmacy
Australia Centre of Excellence, Woolloongabba, Queensland 4102, Australia
- Australian
Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, St Lucia, Queensland 4072, Australia
| | - Suowen Xu
- Aab
Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, United States
| | - Danielle Kamato
- School
of Pharmacy, University of Queensland, Pharmacy
Australia Centre of Excellence, Woolloongabba, Queensland 4102, Australia
- Department
of Pharmacy, Xinhua College of Sun Yat-Sen
University, Tianhe District, Guangzhou, Guangdong Province 510520, China
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Kumar A, Shariff M, Doshi R. Association Between Past Hepatitis B Infection and Ischemic Heart Disease: An Analysis From the 2007-2016 NHANES Data. Am J Med Sci 2020; 360:372-377. [PMID: 32723514 DOI: 10.1016/j.amjms.2020.05.034] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 04/29/2020] [Accepted: 05/20/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Infection is postulated as a possible risk factor for ischemic heart disease with a spiralling body of evidence. Hepatitis B is one of the most comprehensively investigated infection for its association with ischemic heart disease. This study aims at establishing an association between Hepatitis B core antibody status and ischemic heart disease using National Health and Nutrition Examination Survey (NHANES) database. METHODS NHANES data from 2007 to 2016 were used for the present analysis. To identify patients with self-reported coronary heart disease, angina/angina pectoris, myocardial infarction, we examined the answers to questions MCQ160c, MCQ160d, MCQ160e delineated in NHANES data. These questions as described in the NHANES dataset are as follows: MCQ160c-Has a doctor or other health professional ever told you that you had coronary heart disease?, MCQ160d-Has a doctor or other health professional ever told you that you had angina, also called angina pectoris?, MCQ160e- Has a doctor or other health professional ever told you that you had a heart attack also called myocardial infarction?. Next, to identify patients with positive Hepatitis B core antibody, we examined the variable LBXHBC of the NHANES dataset. Baseline characteristics, along with unadjusted and adjusted odds ratio using multivariable logistic regression analysis, of included patients were analyzed for Hepatitis B core antibody and its association with ischemic heart disease. RESULTS A total of 3,248 individuals with ischemic heart disease and 42,345 individuals with no ischemic heart disease were included in the final analysis. Hepatitis B core antibody positive status was associated with lower incidence of ischemic heart disease, adjusted odds ratio of 0.61 (95% confidence interval: 0.41-0.92, P value < 0.02). CONCLUSIONS In conclusion, the present analysis points toward a possible association between past Hepatitis B infection and ischemic heart disease. Hepatitis B infection was associated with a decreased incidence of ischemic heart disease. Further research with better design and possible molecular mechanism is warranted.
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Affiliation(s)
- Ashish Kumar
- Department of Critical Care Medicine, St John's Medical College Hospital, Bangalore, India.
| | - Mariam Shariff
- Department of Critical Care Medicine, St John's Medical College Hospital, Bangalore, India
| | - Rajkumar Doshi
- Department of Internal Medicine, University of Nevada Reno School of Medicine, Reno, Nevada, USA
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Szczuko M, Hawryłkowicz V, Kikut J, Drozd A. The implications of vitamin content in the plasma in reference to the parameters of carbohydrate metabolism and hormone and lipid profiles in PCOS. J Steroid Biochem Mol Biol 2020; 198:105570. [PMID: 31883924 DOI: 10.1016/j.jsbmb.2019.105570] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 12/18/2019] [Accepted: 12/23/2019] [Indexed: 12/12/2022]
Abstract
So far, there have been no analyses of correlations between the level of water-soluble vitamins in women with polycystic ovary syndrome (PCOS) and hormone and lipid profiles as well as carbohydrate metabolism. The unpopular concept that PCOS may also be conditioned by a chronic infection leads to a suspicion that water-soluble vitamins may be involved in the struggle against PCOS. This is why the aim of this research was to determine whether there are any indications that could confirm this hypothesis. The study included 64 women of Caucasian race: 50 patients aged 29.52 ± 7.01 years with PCOS, diagnosed according to the Rotterdam criteria. The control group consisted of 14 women aged 30.23 ± 6.3 years with correct BMI. HPLC Infinity1260 Binary LC (Agilent Technologies, Waldbronn, Germany) was used to analyze nine vitamins. The vitamins were separated using the gradient method, a buffer of 25 mM HK2PO4 with pH equal to 7.0, and 100 % methanol buffer. The acquired results were compared using Statistica 12.0 (Statsoft, Tulsa, Oklahoma, USA). Non-parametric tests were used: Mann-Whitney tests for comparisons between groups (PCOS and control group, CG), in which p < 0.05 was considered statistically significant. Subsequently, we performed a correlation matrix of the biochemical parameters of blood with vitamins at p ≤ 0.05. Higher concentrations of ascorbic acid were observed in PCOS. The content of the remaining vitamins was higher in the control group, and the statistical differences were significant in reference to thiamine, riboflavin, pyridoxine and folic acid in comparison to the control group. A significant positive correlation was observed between vitamin C and testosterone/insulin, another between riboflavin and androstenedione/testosterone, next between biotin and thyrotropic hormone (TSH), between pantothenic acid and dehydroepiandrosteron (DHEA-SO4), and finally between pyridoxine and androstenedione. A negative correlation was observed in the case of niacin with sex hormone binding protein (SHBG) and high density lipoprotein (HDL). Water-soluble vitamins play an important role in the therapy of women with PCOS through the reduction of antioxidative stress and low-intensity inflammation caused by various factors, including chronic infection.
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Affiliation(s)
- Małgorzata Szczuko
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, Poland.
| | - Viktoria Hawryłkowicz
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, Poland.
| | - Justyna Kikut
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, Poland.
| | - Arleta Drozd
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, Poland.
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Inhibition of tRNA Synthetases Induces Persistence in Chlamydia. Infect Immun 2020; 88:IAI.00943-19. [PMID: 31964747 DOI: 10.1128/iai.00943-19] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 01/15/2020] [Indexed: 02/06/2023] Open
Abstract
Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections, and Chlamydia pneumoniae causes community-acquired respiratory infections. In vivo, the host immune system will release gamma interferon (IFN-γ) to combat infection. IFN-γ activates human cells to produce the tryptophan (Trp)-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO). Consequently, there is a reduction in cytosolic Trp in IFN-γ-activated host cells. In evolving to obligate intracellular dependence, Chlamydia has significantly reduced its genome size and content, as it relies on the host cell for various nutrients. Importantly, C. trachomatis and C. pneumoniae are Trp auxotrophs and are starved for this essential nutrient when the human host cell is exposed to IFN-γ. To survive this, chlamydiae enter an alternative developmental state referred to as persistence. Chlamydial persistence is characterized by a halt in the division cycle, aberrant morphology, and, in the case of IFN-γ-induced persistence, Trp codon-dependent changes in transcription. We hypothesize that these changes in transcription are dependent on the particular amino acid starvation state. To investigate the chlamydial response mechanisms acting when other amino acids become limiting, we tested the efficacy of prokaryote-specific tRNA synthetase inhibitors, indolmycin and AN3365, to mimic starvation of Trp and leucine, respectively. We show that these drugs block chlamydial growth and induce changes in morphology and transcription consistent with persistence. Importantly, growth inhibition was reversed when the compounds were removed from the medium. With these data, we find that indolmycin and AN3365 are valid tools that can be used to mimic the persistent state independently of IFN-γ.
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Passos LSA, Lupieri A, Becker-Greene D, Aikawa E. Innate and adaptive immunity in cardiovascular calcification. Atherosclerosis 2020; 306:59-67. [PMID: 32222287 DOI: 10.1016/j.atherosclerosis.2020.02.016] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 01/10/2020] [Accepted: 02/20/2020] [Indexed: 12/19/2022]
Abstract
Despite the focus placed on cardiovascular research, the prevalence of vascular and valvular calcification is increasing and remains a leading contributor of cardiovascular morbidity and mortality. Accumulating studies provide evidence that cardiovascular calcification is an inflammatory disease in which innate immune signaling becomes sustained and/or excessive, shaping a deleterious adaptive response. The triggering immune factors and subsequent inflammatory events surrounding cardiovascular calcification remain poorly understood, despite sustained significant research interest and support in the field. Most studies on cardiovascular calcification focus on innate cells, particularly macrophages' ability to release pro-osteogenic cytokines and calcification-prone extracellular vesicles and apoptotic bodies. Even though substantial evidence demonstrates that macrophages are key components in triggering cardiovascular calcification, the crosstalk between innate and adaptive immune cell components has not been adequately addressed. The only therapeutic options currently used are invasive procedures by surgery or transcatheter intervention. However, no approved drug has shown prophylactic or therapeutic effectiveness. Conventional diagnostic imaging is currently the best method for detecting, measuring, and assisting in the treatment of calcification. However, these common imaging modalities are unable to detect early subclinical stages of disease at the level of microcalcifications; therefore, the vast majority of patients are diagnosed when macrocalcifications are already established. In this review, we unravel the current knowledge of how innate and adaptive immunity regulate cardiovascular calcification; and put forward differences and similarities between vascular and valvular disease. Additionally, we highlight potential immunomodulatory drugs with the potential to target calcification and propose avenues in need of further translational inquiry.
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Affiliation(s)
- Livia S A Passos
- Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Adrien Lupieri
- Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Dakota Becker-Greene
- Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Elena Aikawa
- Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA; Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA; Department of Pathology, Sechenov First Moscow State Medical University, Moscow, 119992, Russia.
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30
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O'Seaghdha CM, Foley RN. Septicemia, Access, Cardiovascular Disease, and Death in Dialysis Patients. Perit Dial Int 2020. [DOI: 10.1177/089686080502500604] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
| | - Robert N. Foley
- Chronic Disease Research Group, Minneapolis, Minnesota, USA
- University of Minnesota, Minneapolis, Minnesota, USA
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31
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Kortesoja M, Trofin RE, Hanski L. A platform for studying the transfer of Chlamydia pneumoniae infection between respiratory epithelium and phagocytes. J Microbiol Methods 2020; 171:105857. [PMID: 32006529 DOI: 10.1016/j.mimet.2020.105857] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 01/13/2020] [Accepted: 01/28/2020] [Indexed: 12/17/2022]
Abstract
The obligate intracellular bacterium, Chlamydia pneumoniae, has been identified as a risk factor for several chronic inflammatory diseases in addition to respiratory tract infections. The dissemination of C. pneumoniae from respiratory tract to secondary sites of infection occurs via infected monocyte / macrophage line cells, in which C. pneumoniae can persist as an antibiotic-refractory phenotype. To allow more detailed studies on the epithelium-monocyte/macrophage transition of the infection, new in vitro bioassays are needed. To this end, a coculture system with human continuous cell lines was established. Respiratory epithelial HL cells were infected with C. pneumoniae and THP-1 monocytes were added into the cultures at 67 h post infection. After a 5 h coculture, THP-1 cells were collected with a biotinylated HLA antibody and streptavidin-coated magnetic beads and C. pneumoniae genome copy numbers in THP-1 determined by quantitative PCR. The assay was optimized for cell densities, incubation time, THP-1 separation technique and buffer composition, and its robustness was demonstrated by a Z' value of 0.6. The mitogen-activated protein kinase (MAPK) inhibitors: SP600125 (JNK inhibitor), SB203580 (p38 inhibitor) and FR180204 (ERK inhibitor) suppressed the transfer of C. pneumoniae from HL to THP-1 cells, making them suitable positive controls for the assay. Based on analysis of separate steps of the process, the MAPK inhibitors suppress the bacterial entry to THP-1 cells. The transfer of C. pneumoniae from epithelium to phagocytes represents a crucial step in the establishment of persistent infections by this pathogen, and the presented methods enables future studies to block this process by therapeutic means.
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Affiliation(s)
- Maarit Kortesoja
- Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014, Finland
| | - Raluca Elena Trofin
- Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014, Finland; Faculty of Pharmacy, University of Bucharest, Bulevardul Regina Elisabeta 4-12, 030018 Bucharest, Romania
| | - Leena Hanski
- Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014, Finland.
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32
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Cheok YY, Lee CYQ, Cheong HC, Looi CY, Wong WF. Chronic Inflammatory Diseases at Secondary Sites Ensuing Urogenital or Pulmonary Chlamydia Infections. Microorganisms 2020; 8:microorganisms8010127. [PMID: 31963395 PMCID: PMC7022716 DOI: 10.3390/microorganisms8010127] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2019] [Revised: 01/02/2020] [Accepted: 01/08/2020] [Indexed: 12/11/2022] Open
Abstract
Chlamydia trachomatis and C. pneumoniae are members of the Chlamydiaceae family of obligate intracellular bacteria. The former causes diseases predominantly at the mucosal epithelial layer of the urogenital or eye, leading to pelvic inflammatory diseases or blindness; while the latter is a major causative agent for pulmonary infection. On top of these well-described diseases at the respective primary infection sites, Chlamydia are notoriously known to migrate and cause pathologies at remote sites of a host. One such example is the sexually acquired reactive arthritis that often occurs at few weeks after genital C. trachomatis infection. C. pneumoniae, on the other hand, has been implicated in an extensive list of chronic inflammatory diseases which include atherosclerosis, multiple sclerosis, Alzheimer’s disease, asthma, and primary biliary cirrhosis. This review summarizes the Chlamydia infection associated diseases at the secondary sites of infection, and describes the potential mechanisms involved in the disease migration and pathogenesis.
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Affiliation(s)
- Yi Ying Cheok
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; (Y.Y.C.); (C.Y.Q.L.); (H.C.C.)
| | - Chalystha Yie Qin Lee
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; (Y.Y.C.); (C.Y.Q.L.); (H.C.C.)
| | - Heng Choon Cheong
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; (Y.Y.C.); (C.Y.Q.L.); (H.C.C.)
| | - Chung Yeng Looi
- School of Biosciences, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Malaysia;
| | - Won Fen Wong
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; (Y.Y.C.); (C.Y.Q.L.); (H.C.C.)
- Correspondence: ; Tel.: +603-7967-6672
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Abstract
Influenza viruses infect the upper respiratory system, causing usually a self-limited disease with mild respiratory symptoms. Acute lung injury, pulmonary microvascular leakage and cardiovascular collapse may occur in severe cases, usually in the elderly or in immunocompromised patients. Acute lung injury is a syndrome associated with pulmonary oedema, hypoxaemia and respiratory failure. Influenza virus primarily binds to the epithelium, interfering with the epithelial sodium channel function. However, the main clinical devastating effects are caused by endothelial dysfunction, thought to be the main mechanism leading to pulmonary oedema, respiratory failure and cardiovascular collapse. A significant association was found between influenza infection and acute myocardial infarction (AMI). The incidence of admission due to AMI during an acute viral infection was six times as high during the 7 days after laboratory confirmation of influenza infection as during the control interval (10-fold in influenza B, 5-fold in influenza A, 3.5-fold in respiratory syncytial virus and 2.7-fold for all other viruses). Our review will focus on the mechanisms responsible for endothelial dysfunction during influenza infection leading to cardiovascular collapse and death.
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Affiliation(s)
- A Peretz
- Clinical Microbiology Laboratory, Baruch Padeh Medical Center, Poriya, Tiberias, Israel
- The Research Institute, Baruch Padeh Medical Center
- Azrieli Faculty of Medicine
| | - M Azrad
- Clinical Microbiology Laboratory, Baruch Padeh Medical Center, Poriya, Tiberias, Israel
- The Research Institute, Baruch Padeh Medical Center
- Azrieli Faculty of Medicine
| | - A Blum
- The Research Institute, Baruch Padeh Medical Center
- Azrieli Faculty of Medicine
- Vascular and Regenerative Research Laboratory, Bar-Ilan University, Galilee, Safed, Israel
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Nagarajan UM, Sikes JD, Burris RL, Jha R, Popovic B, Fraungruber P, Hennings L, Haggerty CL, Nagarajan S. Genital Chlamydia infection in hyperlipidemic mouse models exacerbates atherosclerosis. Atherosclerosis 2019; 290:103-110. [PMID: 31604170 DOI: 10.1016/j.atherosclerosis.2019.09.021] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Revised: 09/11/2019] [Accepted: 09/26/2019] [Indexed: 01/21/2023]
Abstract
BACKGROUND AND AIMS Atherosclerosis is a chronic inflammatory disease, and recent studies have shown that infection at remote sites can contribute to the progression of atherosclerosis in hyperlipidemic mouse models. In this report, we tested the hypothesis that genital Chlamydia infection could accelerate the onset and progression of atherosclerosis. METHODS Apolipoprotein E (Apoe-/-) and LDL receptor knockout (Ldlr-/-) mice on a high-fat diet were infected intra-vaginally with Chlamydia muridarum. Atherosclerotic lesions on the aortic sinuses and in the descending aorta were assessed at 8-weeks post-infection. Systemic, macrophage, and vascular site inflammatory responses were assessed and quantified. RESULTS Compared to the uninfected groups, infected Apoe-/- and Ldlr-/- mice developed significantly more atherosclerotic lesions in the aortic sinus and in the descending aorta. Increased lesions were associated with higher circulating levels of serum amyloid A-1, IL-1β, TNF-α, and increased VCAM-1 expression in the aortic sinus, suggesting an association with inflammatory responses observed during C. muridarum infection. Genital infection courses were similar in Apoe-/-, Ldlr-/-, and wild type mice. Further, Apoe-/- mice developed severe uterine pathology with increased dilatations. Apoe-deficiency also augmented cytokine/chemokine response in C. muridarum infected macrophages, suggesting that the difference in macrophage response could have contributed to the genital pathology in Apoe-/- mice. CONCLUSIONS Overall, these studies demonstrate that genital Chlamydia infection exacerbates atherosclerotic lesions in hyperlipidemic mouse and suggest a novel role for Apoe in full recovery of uterine anatomy after chlamydial infection.
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Affiliation(s)
- Uma M Nagarajan
- Department of Pediatrics and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR, USA
| | - James D Sikes
- Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR, USA
| | - Ramona L Burris
- Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR, USA
| | - Rajneesh Jha
- Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR, USA
| | - Branimir Popovic
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Pamelia Fraungruber
- Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Leah Hennings
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Catherine L Haggerty
- Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
| | - Shanmugam Nagarajan
- Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR, USA; Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Di Pietro M, Filardo S, Romano S, Sessa R. Chlamydia trachomatis and Chlamydia pneumoniae Interaction with the Host: Latest Advances and Future Prospective. Microorganisms 2019; 7:microorganisms7050140. [PMID: 31100923 PMCID: PMC6560445 DOI: 10.3390/microorganisms7050140] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 05/07/2019] [Accepted: 05/14/2019] [Indexed: 12/27/2022] Open
Abstract
Research in Chlamydia trachomatis and Chlamydia pneumoniae has gained new traction due to recent advances in molecular biology, namely the widespread use of the metagenomic analysis and the development of a stable genomic transformation system, resulting in a better understanding of Chlamydia pathogenesis. C. trachomatis, the leading cause of bacterial sexually transmitted diseases, is responsible of cervicitis and urethritis, and C. pneumoniae, a widespread respiratory pathogen, has long been associated with several chronic inflammatory diseases with great impact on public health. The present review summarizes the current evidence regarding the complex interplay between C. trachomatis and host defense factors in the genital micro-environment as well as the key findings in chronic inflammatory diseases associated to C. pneumoniae.
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Affiliation(s)
- Marisa Di Pietro
- Department of Public Health and Infectious Diseases, Section of Microbiology, University of Rome "Sapienza", 00185 Rome, Italy.
| | - Simone Filardo
- Department of Public Health and Infectious Diseases, Section of Microbiology, University of Rome "Sapienza", 00185 Rome, Italy.
| | - Silvio Romano
- Cardiology, Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
| | - Rosa Sessa
- Department of Public Health and Infectious Diseases, Section of Microbiology, University of Rome "Sapienza", 00185 Rome, Italy.
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Gomez LM, Anton L, Srinivas SK, Elovitz MA, Parry S. Low-Dose Aspirin May Prevent Trophoblast Dysfunction in Women With Chlamydia Pneumoniae Infection. Reprod Sci 2018; 26:1449-1459. [PMID: 30572799 DOI: 10.1177/1933719118820468] [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: 12/18/2022]
Abstract
OBJECTIVE Previously, we demonstrated that live Chlamydia pneumoniae (Cp) impaired extravillous trophoblast (EVT) viability and invasion and that Cp DNA was detected in placentas from cases with preeclampsia. We sought to elucidate whether (1) inactive forms of Cp also affect EVT function; (2) potential therapeutic interventions protect against the effects of Cp; and (3) anti-Cp antibodies are associated with preeclampsia. METHODS Human first-trimester EVTs were infected with ultraviolet light-inactivated Cp. Subgroups of EVTs were pretreated with low-dose acetyl-salicylic acid (ASA), dexamethasone, heparin, and indomethacin. We conducted functional assays after infection with inactivated Cp and measured interleukin 8 (IL8), C-reactive protein (CRP), heat shock protein 60 (HSP60), and tumor necrosis factor-α (TNFα) in culture media. We measured anti-Cp IgG serum levels from women who developed preeclampsia (N = 105) and controls (N = 121). RESULTS Inactivated Cp reduced EVT invasion when compared to noninfected cells (P < .00001) without adversely affecting cell viability. Increased levels of IL8, CRP, HSP60, and TNFα were detected in EVTs infected with inactivated Cp compared to noninfected cells (P < .0001). Only pretreatment with low-dose ASA prevented reduced EVT invasion and decreased release of inflammatory mediators (P < .01). Elevated anti-Cp IgG antibodies were more prevalent in serum from cases with preeclampsia compared to controls (67/105 vs 53/121; adjusted P = .013); elevated IgG correlated significantly with elevated serum CRP and elevated soluble fms-like tyrosine kinase-1-placental growth factor ratio. CONCLUSION Inactivated Cp induces decreased EVT invasion and a proinflammatory response; these effects were abrogated by pretreatment with low-dose ASA. Our results suggest an association between Cp infection, trophoblast dysfunction, and preeclampsia.
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Affiliation(s)
- Luis M Gomez
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, INOVA Health System, Falls Church, VA, USA
| | - Lauren Anton
- Maternal and Child Health Research Program, University of Pennsylvania, Philadelphia, PA, USA
| | - Shindu K Srinivas
- Maternal and Child Health Research Program, University of Pennsylvania, Philadelphia, PA, USA.,Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Michal A Elovitz
- Maternal and Child Health Research Program, University of Pennsylvania, Philadelphia, PA, USA.,Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Samuel Parry
- Maternal and Child Health Research Program, University of Pennsylvania, Philadelphia, PA, USA.,Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Characterization of Chlamydial Rho and the Role of Rho-Mediated Transcriptional Polarity during Interferon Gamma-Mediated Tryptophan Limitation. Infect Immun 2018; 86:IAI.00240-18. [PMID: 29712731 DOI: 10.1128/iai.00240-18] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 04/27/2018] [Indexed: 01/15/2023] Open
Abstract
As an obligate intracellular, developmentally regulated bacterium, Chlamydia is sensitive to amino acid fluctuations within its host cell. When human epithelial cells are treated with the cytokine interferon gamma (IFN-γ), the tryptophan (Trp)-degrading enzyme, indoleamine-2,3-dioxygenase, is induced. Chlamydiae within such cells are starved for Trp and enter a state of so-called persistence. Chlamydia lacks the stringent response used by many eubacteria to respond to this stress. Unusually, chlamydial transcription is globally elevated during Trp starvation with transcripts for Trp codon-containing genes disproportionately increased. Yet, the presence of Trp codons destabilized 3' ends of transcripts in operons or large genes. We initially hypothesized that ribosome stalling on Trp codons rendered the 3' ends sensitive to RNase activity. The half-life of chlamydial transcripts containing different numbers of Trp codons was thus measured in untreated and IFN-γ-treated infected cells to determine whether Trp codons influenced the stability of transcripts. However, no effect of Trp codon content was detected. Therefore, we investigated whether Rho-dependent transcription termination could play a role in mediating transcript instability. Rho is expressed as a midcycle gene product, interacts with itself as predicted, and is present in all chlamydial species. Inhibition of Rho via the Rho-specific antibiotic, bicyclomycin, and overexpression of Rho are detrimental to chlamydiae. Finally, when we measured transcript abundance 3' to Trp codons in the presence of bicyclomycin, we observed that transcript abundance increased. These data are the first to demonstrate the importance of Rho in Chlamydia and the role of Rho-dependent transcription polarity during persistence.
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Sessa R, Pietro MDI, Schiavoni G, Galdiero M, Cipriani P, Romano S, Zagaglia C, Santino I, Faccilongo S, Piano MD. Chlamydia Pneumoniae in Asymptomatic Carotid Atherosclerosis. Int J Immunopathol Pharmacol 2018. [DOI: 10.1177/205873920601900111] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
We evaluated, in 415 patients with asymptomatic carotid atherosclerosis: (i) the prevalence of C. pneumoniae DNA in atherosclerotic carotid plaques and peripheral blood mononuclear cells (PBMC); (ii) the distribution of C. pneumoniae in atherosclerotic carotid plaques and PBMC from the same patients; (iii) the correlation between circulating anti-chlamydial antibodies and the presence of C. pneumoniae DNA. Overall, 160 atherosclerotic carotid plaques and 174 PBMC specimens from patients with asymptomatic carotid atherosclerosis were examined by ompA nested touchdown PCR for presence of C. pneumoniae. In addition, C. pneumoniae DNA was detected in 81 specimens of atherosclerotic carotid plaque and PBMC obtained from the same patients. C. pneumoniae DNA was found in 36.9% of atherosclerotic carotid plaques and in 40.2% of PBMC specimens examined (P=NS). With regard to 81 patients, C. pneumoniae DNA was detected in 27.2% of atherosclerotic carotid plaques and in 44.4% of PBMC specimens (P=0.05). In 18 patients, the presence of C. pneumoniae DNA in PBMC specimens and atherosclerotic carotid plaques coincided (P=0.005). No statistically significant association was found between anti-C pneumoniae antibodies (IgG and IgA) and positive PCR results. In conclusion, our results suggest that the detection of C. pneumoniae DNA in PBMC specimens seems to be a first-choice method to identify the patients at risk for endovascular chlamydial infection.
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Affiliation(s)
- R. Sessa
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - M. DI Pietro
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - G. Schiavoni
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - M. Galdiero
- Department of Experimental Medicine, Second University of Naples, Naples, Italy
| | - P. Cipriani
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - S. Romano
- Department of Internal Medicine, Cardiology, University of L'Aquila, Italy
| | - C. Zagaglia
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - I. Santino
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - S. Faccilongo
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - M. Del Piano
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
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Wallet SM, Puri V, Gibson FC. Linkage of Infection to Adverse Systemic Complications: Periodontal Disease, Toll-Like Receptors, and Other Pattern Recognition Systems. Vaccines (Basel) 2018; 6:E21. [PMID: 29621153 PMCID: PMC6027258 DOI: 10.3390/vaccines6020021] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 03/25/2018] [Accepted: 03/30/2018] [Indexed: 12/13/2022] Open
Abstract
Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs) that provide innate immune sensing of conserved pathogen-associated molecular patterns (PAMPs) to engage early immune recognition of bacteria, viruses, and protozoa. Furthermore, TLRs provide a conduit for initiation of non-infectious inflammation following the sensing of danger-associated molecular patterns (DAMPs) generated as a consequence of cellular injury. Due to their essential role as DAMP and PAMP sensors, TLR signaling also contributes importantly to several systemic diseases including cardiovascular disease, diabetes, and others. The overlapping participation of TLRs in the control of infection, and pathogenesis of systemic diseases, has served as a starting point for research delving into the poorly defined area of infection leading to increased risk of various systemic diseases. Although conflicting studies exist, cardiovascular disease, diabetes, cancer, rheumatoid arthritis, and obesity/metabolic dysfunction have been associated with differing degrees of strength to infectious diseases. Here we will discuss elements of these connections focusing on the contributions of TLR signaling as a consequence of bacterial exposure in the context of the oral infections leading to periodontal disease, and associations with metabolic diseases including atherosclerosis and type 2 diabetes.
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Affiliation(s)
- Shannon M Wallet
- Department of Oral Biology, College of Dental Medicine, University of Florida, Gainesville, FL 32610, USA.
| | - Vishwajeet Puri
- Department of Biomedical Sciences and Diabetes Institute, Ohio University, Athens, OH 45701, USA.
| | - Frank C Gibson
- Department of Oral Biology, College of Dental Medicine, University of Florida, Gainesville, FL 32610, USA.
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40
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Sima P, Vannucci L, Vetvicka V. Atherosclerosis as autoimmune disease. ANNALS OF TRANSLATIONAL MEDICINE 2018; 6:116. [PMID: 29955576 DOI: 10.21037/atm.2018.02.02] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
No attention is usually focused on the possible involvement of immune mechanisms, particularly of autoimmunity, on the development and progress of atherosclerosis. The pioneering work occurring almost 50 years ago was overlooked, and the idea of atherosclerosis as an autoimmune disease only started gaining traction about 10 years ago. Our review discusses the recent findings and offers insights into the possibility that alterations of the immune system play a significant role in the development of atherosclerosis.
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Affiliation(s)
- Petr Sima
- Institute of Microbiology, Laboratory of Immunotherapy, Prague, Czech
| | - Luca Vannucci
- Institute of Microbiology, Laboratory of Immunotherapy, Prague, Czech
| | - Vaclav Vetvicka
- University of Louisville, Department of Pathology, Louisville, KY, USA
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41
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Liu J, Miao G, Wang B, Zheng N, Ma L, Chen X, Wang G, Zhao X, Zhang L, Zhang L. Chlamydia pneumoniae infection promotes monocyte transendothelial migration by increasing vascular endothelial cell permeability via the tyrosine phosphorylation of VE-cadherin. Biochem Biophys Res Commun 2018; 497:742-748. [PMID: 29462613 DOI: 10.1016/j.bbrc.2018.02.145] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Accepted: 02/16/2018] [Indexed: 11/28/2022]
Abstract
Migration of monocytes into the subendothelial layer of the intima is one of the critical events in early atherosclerosis. Chlamydia pneumoniae (C. pneumoniae) infection has been shown to promote monocyte transendothelial migration (TEM). However, the exact mechanisms have not yet been fully clarified. In this study, we tested the hypothesis that C. pneumoniae infection increases vascular endothelial cell (VEC) permeability and subsequent monocyte TEM through stimulating the tyrosine phosphorylation of vascular endothelial-cadherin (VE-cadherin). Here, we demonstrated that C. pneumoniae infection promoted monocyte TEM in a TEM assay possibly by increasing the permeability of a VEC line EA.hy926 cell as assessed by measuring the passage of FITC-BSA across a VEC monolayer. Subsequently, Western blot analysis showed that C. pneumoniae infection induced VE-cadherin internalization. Our further data revealed that Src-mediated VE-cadherin phosphorylation at Tyr658 was involved in C. pneumoniae infection-induced internalization of VE-cadherin, VEC hyperpermeability and monocyte TEM. Taken together, our data indicate that C. pneumoniae infection promotes monocyte TEM by increasing VEC permeability via the tyrosine phosphorylation and internalization of VE-cadherin in VECs.
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Affiliation(s)
- Jingya Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Guolin Miao
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Beibei Wang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Ningbo Zheng
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Lu Ma
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Xiaoyu Chen
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Guangyan Wang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Xi Zhao
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Lijun Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
| | - Lijun Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
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42
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Paplińska-Goryca M, Rubinsztajn R, Nejman-Gryz P, Przybyłowski T, Krenke R, Chazan R. The association between serological features of chronic Chlamydia pneumoniae infection and markers of systemic inflammation and nutrition in COPD patients. Scandinavian Journal of Clinical and Laboratory Investigation 2017; 77:644-650. [PMID: 29069917 DOI: 10.1080/00365513.2017.1393694] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Chlamydia pneumoniae is an obligatory human pathogen involved in lower and upper airway infections, including pneumonia, bronchitis. Asymptomatic C. pneumoniae carriage is also relatively common. The association of C. pneumoniae infections with the chronic obstructive pulmonary disease (COPD) course is unclear. OBJECTIVES The aim of the study was to investigate the association between chronic C. pneumoniae infection and clinical features of COPD, markers of inflammation and metabolic dysfunction. PATIENTS AND METHODS The study included 59 patients with stable COPD who had no, or had ≥2 acute exacerbations during last year. The level of IgA and IgG antibody against C. pneumoniae, IL-6, IL-8, resistin, insulin, adiponectin and acyl ghrelin was measured in serum by enzyme-linked immunosorbent assay (ELISA). RESULTS No differences in clinical and functional data were observed between COPD patients without serological features of C. pneumoniae infection and chronic C. pneumoniae infection. The level of anti C. pneumoniae IgA significantly correlated with IL-8, IL-6, resistin concentration in group of frequent exacerbators. IgG level correlated negatively with acetyl ghrelin and body mass index (BMI) in patients without frequent exacerbations, in contrast to frequent COPD exacerbation group where significant correlations between IgG level and BMI was demonstrated. Serum IL-6 correlated positively with resistin and insulin and negatively with adiponectin in group of patients with serological features of chronic C. pneumoniae infection only. CONCLUSIONS Our study showed that chronic C. pneumoniae infection does not influence the clinical course of COPD in the both study groups. Chronic C. pneumoniae infections might be associated with a distinct COPD phenotype that affects metabolic dysfunction.
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Affiliation(s)
- Magdalena Paplińska-Goryca
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
| | - Renata Rubinsztajn
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
| | - Patrycja Nejman-Gryz
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
| | - Tadeusz Przybyłowski
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
| | - Rafał Krenke
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
| | - Ryszarda Chazan
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
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43
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Romano S, Fratini S, Di Pietro M, Schiavoni G, Nicoletti M, Chiarotti F, Del Piano M, Penco M, Sessa R. Chlamydia Pneumoniae Infection in Patients with Acute Coronary Syndrome: A Clinical and Serological 1-Year Follow-Up. Int J Immunopathol Pharmacol 2017; 17:209-18. [PMID: 15171822 DOI: 10.1177/039463200401700213] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The role of Chlamydia pneumoniae infection in pathogenesis and prognostic stratification of patients with acute coronary syndromes is still unclear. However, a limitation of many studies is the evaluation of the long-term prognostic role of a sample obtained during the acute phase, whereas the assessment of the temporal trend of antibody titers could be more useful. One-hundred and fourteen consecutive patients with acute coronary syndromes (71 with acute myocardial infarction and 43 with unstable angina) were studied. Blood samples were obtained immediately after hospital admission and 1, 3, 6 and 12 months after the acute event. The microimmunofluorescence test was used to detect C. pneumoniae specific antibodies. The incidence of new coronary events (death, myocardial infarction, recurrent angina) was recorded during the 1-year follow-up period. No significant difference was found between patients with (n = 35) or without (n = 79) new coronary events (N.C.E.) regarding baseline and serial values of C. pneumoniae antibodies. The rate of high titers at any time of follow-up was also similar in the two groups: IgG ≥1:512 were present in 52%, 64%, 55% and 32% of N.C.E.+ patients, and in 48%, 54%, 52% and 36% of N.C.E.- patients at 1, 3, 6 and 12 months respectively; IgA ≥ 1:256 were present in 26%, 23%, 30% and 23% of N.C.E.+ patients and in 20%, 30%, 25% and 19% of N.C.E.- patients at 1, 3, 6 and 12 months respectively. Our data indicate that elevated titers of C. pneumoniae antibodies, even with a serial 1-year evaluation, are not a predictor of future coronary events in patients with acute myocardial infarction or unstable angina.
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Affiliation(s)
- S Romano
- Dept Internal Medicine, Cardiology, University of L'Aquila, L'Aquila, Italy
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Sethi NJ, Safi S, Korang SK, Hróbjartsson A, Skoog M, Gluud C, Jakobsen JC. Antibiotics for secondary prevention of coronary heart disease. Hippokratia 2017. [DOI: 10.1002/14651858.cd003610.pub3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- Naqash J Sethi
- Department 7812, Rigshospitalet, Copenhagen University Hospital; Copenhagen Trial Unit, Centre for Clinical Intervention Research; Blegdamsvej 9 Copenhagen Denmark 2100
| | - Sanam Safi
- Department 7812, Rigshospitalet, Copenhagen University Hospital; Copenhagen Trial Unit, Centre for Clinical Intervention Research; Blegdamsvej 9 Copenhagen Denmark 2100
| | - Steven Kwasi Korang
- Department 7812, Rigshospitalet, Copenhagen University Hospital; Copenhagen Trial Unit, Centre for Clinical Intervention Research; Blegdamsvej 9 Copenhagen Denmark 2100
| | - Asbjørn Hróbjartsson
- Odense University Hospital and University of Southern Denmark; Center for Evidence-Based Medicine; Sdr. Boulevard 29, Gate 50 (Videncenteret) Odense C Denmark 5000
| | - Maria Skoog
- Barsebäcksvägen 39 Löddeköpinge Sweden 24630
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital; The Cochrane Hepato-Biliary Group; Blegdamsvej 9 Copenhagen Denmark DK-2100
| | - Janus C Jakobsen
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital; The Cochrane Hepato-Biliary Group; Blegdamsvej 9 Copenhagen Denmark DK-2100
- Holbaek Hospital; Department of Cardiology; Holbaek Denmark 4300
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45
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Cao J, Mao Y, Dong B, Guan W, Shi J, Wang S. Detection of specific Chlamydia pneumoniae and cytomegalovirus antigens in human carotid atherosclerotic plaque in a Chinese population. Oncotarget 2017; 8:55435-55442. [PMID: 28903431 PMCID: PMC5589670 DOI: 10.18632/oncotarget.19314] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 06/04/2017] [Indexed: 12/04/2022] Open
Abstract
To explore the relationship between certain pathogens, such as chlamydia pneumonia (Cpn) and cytomegalovirus (CMV), and carotid atherosclerosis (AS) in a Chinese population.Twenty-five carotid atherosclerotic stenosis patients from the Beijing Tiantan Hospital (affiliated with Capital Medical University) participated in the study. After undergoing digital subtraction angiography (DSA) and/or computed tomography angiography (CTA), the degree of carotid artery stenosis was over 70% in all cases, and the patients underwent carotid endarterectomy. Plaque specimens were obtained during surgery. The streptavidin-peroxidase (SP) method was used to test the Cpn and CMV antigens in the specimens, and the relationship between the Cpn and CMV pathogen infections and AS was analyzed based on the test results. In the group of 25 carotid atherosclerotic specimens, the detection rate of the Cpn-specific antigens was 84.0% (21/25). In the control group, the detection rate was 13.3% (2/15) in the ascending aortic intima. Thus, the between-group difference was significant (P<0.01). The CMV-specific antigen detection rate was 72.0% (18/25) using the same experimental group specimens, and the detection rate was zero in the control group. Thus, there were significant between-group differences (P<0.01). Due to the high detection rate of Cpn- and CMV-specific antigens in carotid atherosclerotic plaque in a Chinese population, it can be inferred that pathogens such as Cpn and CMV are one factor associated with carotid atherosclerosis.
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Affiliation(s)
- Jiachao Cao
- Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Yumin Mao
- Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Bo Dong
- Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Wei Guan
- Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Jia Shi
- Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Suinuan Wang
- Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
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Dahal U, Sharma D, Dahal K. An Unsettled Debate About the Potential Role of Infection in Pathogenesis of Atherosclerosis. J Clin Med Res 2017; 9:547-554. [PMID: 28611853 PMCID: PMC5458650 DOI: 10.14740/jocmr3032w] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/12/2017] [Indexed: 12/12/2022] Open
Abstract
Association of infection with atherosclerosis is by no means new. Several sero-epidemiological and pathologic studies as well as animal models have shown a link between infection and atherosclerosis. Exciting discoveries in recent times related to role of inter-individual genetic variation in modulating inflammatory response to infection have reignited the enthusiasm in proving a causal link between infection and atherosclerosis. The purpose of this article was to review and analyze the available evidence linking infection with atherosclerosis.
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Affiliation(s)
- Udip Dahal
- Department of Medicine, University of Utah, 50 N Medical Drive, Salt Lake City, UT, USA
| | - Dikshya Sharma
- Department of Internal Medicine, Staten Island University Hospital, 475 Seaview Avenue, Staten Island, NY, USA
| | - Kumud Dahal
- Department of Infectious Disease, University of Illinois College of Medicine at Peoria, 1 Illinoi Drive, Peoria, IL, USA
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Kalayci F, Ozdemir A, Saribas S, Yuksel P, Ergin S, Kuskucu AM, Poyraz CA, Balcioglu I, Alpay N, Kurt A, Sezgin Z, Kocak BT, Icel RS, Can G, Tokman HB, Kocazeybek B. The relationship of Chlamydophila pneumoniae with schizophrenia: The role of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in this relationship. Rev Argent Microbiol 2017; 49:39-49. [PMID: 28256360 DOI: 10.1016/j.ram.2016.09.009] [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: 09/09/2015] [Revised: 09/06/2016] [Accepted: 09/12/2016] [Indexed: 10/20/2022] Open
Abstract
Several pathogens have been suspected of playing a role in the pathogenesis of schizophrenia. Chronic inflammation has been proposed to occur as a result of persistent infection caused by Chlamydophila pneumoniae cells that reside in brain endothelial cells for many years. It was recently hypothesized that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) may play prominent roles in the development of schizophrenia. NT-3 and BDNF levels have been suggested to change in response to various manifestations of infection. Therefore, we aimed to elucidate the roles of BDNF and NT3 in the schizophrenia-C. pneumoniae infection relationship. RT-PCR, immunofluorescence and ELISA methods were used. Fifty patients suffering from schizophrenia and 35 healthy individuals were included as the patient group (PG) and the healthy control group (HCG), respectively. We detected persistent infection in 14 of the 50 individuals in the PG and in 1 of the 35 individuals in the HCG. A significant difference was found between the two groups (p<0.05). Twenty-two individuals in the PG and 13 in the HCG showed seropositivity for past C. pneumoniae infection, and no difference was observed between the groups (p>0.05). C. pneumoniae DNA was not detected in any group. A significant difference in NT-3 levels was observed between the groups, with very low levels in the PG (p<0.001). A significant difference in BDNF levels was also found, with lower levels in the PG (p<0.05). The mean serum NT-3 level was higher in the PG cases with C. pneumoniae seropositivity than in seronegative cases; however, this difference was not statistically significant (p>0.05). In conclusion, we suggest that NT-3 levels during persistent C. pneumoniae infection may play a role in this relationship.
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Affiliation(s)
- Fatma Kalayci
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Armagan Ozdemir
- T.C. Health Ministry Bakirkoy Mental Health and Neurology Training and Research Hospital Psychiatry Clinic, Istanbul, Turkey
| | - Suat Saribas
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Pelin Yuksel
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Sevgi Ergin
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Ali Mert Kuskucu
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Cana Aksoy Poyraz
- Istanbul University, Cerrahpasa Medical Faculty, Department of Psychiatry, Istanbul, Turkey
| | - Ibrahim Balcioglu
- Istanbul University, Cerrahpasa Medical Faculty, Department of Psychiatry, Istanbul, Turkey
| | - Nihat Alpay
- T.C. Health Ministry Bakirkoy Mental Health and Neurology Training and Research Hospital Psychiatry Clinic, Istanbul, Turkey
| | - Aykut Kurt
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Zeynep Sezgin
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Biochemistry, Istanbul, Turkey
| | - Banu Tufan Kocak
- T.C. Health Ministry Erenkoy Mental Health and Neurology Training and Research Hospital, Istanbul, Turkey
| | - Rana Sucu Icel
- T.C. Health Ministry, Sisli Etfal Education and Research Hospital, Department of Blood Center, Istanbul, Turkey
| | - Gunay Can
- Istanbul University, Cerrahpasa Medical Faculty, Department of Public Health, Istanbul, Turkey
| | - Hrisi Bahar Tokman
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Bekir Kocazeybek
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey.
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High rate of in-stent restenosis after coronary intervention in carriers of the mutant mannose-binding lectin allele. BMC Cardiovasc Disord 2017; 17:4. [PMID: 28056798 PMCID: PMC5217188 DOI: 10.1186/s12872-016-0440-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 12/08/2016] [Indexed: 11/10/2022] Open
Abstract
Background In-stent restenosis occurs in 10–30% of patients following bare metal stent (BMS) implantation and has various risk factors. Mannose-binding lectin (MBL) is known to have effect on the progression of atherosclerosis. Single nucleotide polymorphisms (SNP) of the MBL2 gene intron 1 (codon 52, 54, 57) are known to modulate the bioavailability of the MBL protein. Our aim was to identify the association of these polymorphisms of the MBL gene in the occurrence of in-stent restenosis after coronary artery bare metal stent implantation. Methods In a non-randomized prospective study venous blood samples were collected after recoronarography from 225 patients with prior BMS implantation. Patients were assigned to diffuse restenosis group and control group based on the result of the coronarography. MBL genotypes were determined using quantitative real-time PCR. Proportion of different genotypes was compared and adjusted with traditional risk factors using multivariate logistic regression. Results Average follow-up time was 1.0 (+ − 1.4) year in the diffuse restenosis group (N = 117) and 2.7 (+ − 2.5) years in the control group (N = 108). The age, gender distribution and risk status was not different between study groups. Proportion of the MBL variant genotype was 26.8% (29 vs. 79 normal homozygous) in the control group and 39.3% (46 vs. 71 normal homozygous) in the restenosis group (p = 0.04). In multivariate analysis the mutant allele was an independent risk factor (OR = 1.96, p = 0.03) of in-stent restenosis. Conclusions MBL polymorphisms are associated with higher incidence of development of coronary in-stent restenosis. The attenuated protein function in the mutant allelic genotype may represent the underlying mechanism.
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Sharma L, Losier A, Tolbert T, Dela Cruz CS, Marion CR. Atypical Pneumonia: Updates on Legionella, Chlamydophila, and Mycoplasma Pneumonia. Clin Chest Med 2016; 38:45-58. [PMID: 28159161 DOI: 10.1016/j.ccm.2016.11.011] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Community-acquired pneumonia (CAP) has multiple causes and is associated with illness that requires admission to the hospital and mortality. The causes of atypical CAP include Legionella species, Chlamydophila, and Mycoplasma. Atypical CAP remains a diagnostic challenge and, therefore, likely is undertreated. This article reviews the advancements in the evaluation and treatment of patients and discusses current conflicts and controversies of atypical CAP.
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Affiliation(s)
- Lokesh Sharma
- Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, 300 Cedar Street, TAC S440, New Haven, CT 06510, USA
| | - Ashley Losier
- Department of Internal Medicine, Norwalk Hospital, 34 Maple Street, Norwalk, CT 06856, USA
| | - Thomas Tolbert
- Department of Internal Medicine, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06510, USA
| | - Charles S Dela Cruz
- Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, 300 Cedar Street, TAC S440, New Haven, CT 06510, USA
| | - Chad R Marion
- Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, 300 Cedar Street, TAC S440, New Haven, CT 06510, USA.
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50
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Queiroz MAF, Gomes STM, Almeida NCC, Souza MIM, Costa SRCF, Hermes RB, Lima SS, Zaninotto MM, Fossa MAA, Maneschy MA, Martins-Feitosa RN, Azevedo VN, Machado LFA, Ishak MOG, Ishak R, Vallinoto ACR. Mannose-binding lectin 2 (Mbl2) gene polymorphisms are related to protein plasma levels, but not to heart disease and infection by Chlamydia. ACTA ACUST UNITED AC 2016; 49:e5519. [PMID: 27982280 PMCID: PMC5188863 DOI: 10.1590/1414-431x20165519] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 09/01/2016] [Indexed: 01/20/2023]
Abstract
The presence of the single nucleotide polymorphisms in exon 1 of the mannose-binding lectin 2 (MBL2) gene was evaluated in a sample of 159 patients undergoing coronary artery bypass surgery (71 patients undergoing valve replacement surgery and 300 control subjects) to investigate a possible association between polymorphisms and heart disease with Chlamydia infection. The identification of the alleles B and D was performed using real time polymerase chain reaction (PCR) and of the allele C was accomplished through PCR assays followed by digestion with the restriction enzyme. The comparative analysis of allelic and genotypic frequencies between the three groups did not reveal any significant difference, even when related to previous Chlamydia infection. Variations in the MBL plasma levels were influenced by the presence of polymorphisms, being significantly higher in the group of cardiac patients, but without representing a risk for the disease. The results showed that despite MBL2 gene polymorphisms being associated with the protein plasma levels, the polymorphisms were not enough to predict the development of heart disease, regardless of infection with both species of Chlamydia.
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Affiliation(s)
- M A F Queiroz
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil
| | - S T M Gomes
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil
| | - N C C Almeida
- Fundação de Hematologia e Hemoterapia do Pará, Belém, PA, Brasil
| | - M I M Souza
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil
| | - S R C F Costa
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil
| | - R B Hermes
- Fundação de Hematologia e Hemoterapia do Pará, Belém, PA, Brasil
| | - S S Lima
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil
| | - M M Zaninotto
- Hospital de Clínicas Gaspar Vianna, Belém, PA, Brasil
| | - M A A Fossa
- Hospital Beneficência Portuguesa, Belém, PA, Brasil
| | - M A Maneschy
- Hospital Beneficência Portuguesa, Belém, PA, Brasil
| | - R N Martins-Feitosa
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil
| | - V N Azevedo
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil
| | - L F A Machado
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil
| | - M O G Ishak
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil
| | - R Ishak
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil
| | - A C R Vallinoto
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil
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