Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic Syndrome

Atrial fibrillation (AF) and cardiometabolic syndrome (CMS) have been linked to inflammation and fibrosis. However, it is still unknown which inflammatory cytokines contribute to the pathogenesis of AF. Furthermore, cardiometabolic syndrome (CMS) risk factors such as obesity, hypertension, insulin r...

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Main Authors: Hana A. Itani, Miran A. Jaffa, Joseph Elias, Mohammad Sabra, Patrick Zakka, Jad Ballout, Amira Bekdash, Rand Ibrahim, Moustafa Al Hariri, Mirna Ghemrawi, Bernard Abi-Saleh, Maurice Khoury, Samir Alam, Rami Mahfouz, Ayad A. Jaffa, Sami T. Azar, Marwan M. Refaat
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-12-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2020.613271/full
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author Hana A. Itani
Hana A. Itani
Miran A. Jaffa
Joseph Elias
Mohammad Sabra
Patrick Zakka
Jad Ballout
Amira Bekdash
Rand Ibrahim
Moustafa Al Hariri
Mirna Ghemrawi
Bernard Abi-Saleh
Maurice Khoury
Samir Alam
Rami Mahfouz
Ayad A. Jaffa
Sami T. Azar
Marwan M. Refaat
Marwan M. Refaat
author_facet Hana A. Itani
Hana A. Itani
Miran A. Jaffa
Joseph Elias
Mohammad Sabra
Patrick Zakka
Jad Ballout
Amira Bekdash
Rand Ibrahim
Moustafa Al Hariri
Mirna Ghemrawi
Bernard Abi-Saleh
Maurice Khoury
Samir Alam
Rami Mahfouz
Ayad A. Jaffa
Sami T. Azar
Marwan M. Refaat
Marwan M. Refaat
author_sort Hana A. Itani
collection DOAJ
description Atrial fibrillation (AF) and cardiometabolic syndrome (CMS) have been linked to inflammation and fibrosis. However, it is still unknown which inflammatory cytokines contribute to the pathogenesis of AF. Furthermore, cardiometabolic syndrome (CMS) risk factors such as obesity, hypertension, insulin resistance/glucose intolerance are also associated with inflammation and increased level of cytokines and adipokines. We hypothesized that the inflammatory immune response is exacerbated in patients with both AF and CMS compared to either AF or CMS alone. We investigated inflammatory cytokines and fibrotic markers as well as cytokine genetic profiles in patients with lone AF and CMS. CMS, lone AF patients, patients with both lone AF and CMS, and control patients were recruited. Genetic polymorphisms in inflammatory and fibrotic markers were assessed. Serum levels of connective tissue growth factor (CTGF) were tested along with other inflammatory markers including platelet-to-lymphocyte ratio (PLR), monocyte-to-HDL ratio (MHR) in three groups of AF+CMS, AF, and CMS patients. There was a trend in the CTGF levels for statistical significance between the AF and AF+CMS group (P = 0.084). Genotyping showed high percentages of patients in all groups with high secretor genotypes of Interleukin-6 (IL-6) (P = 0.037). Genotyping of IFN-γ and IL-10 at high level showed an increase in expression in the AF + CMS group compared to AF and CMS alone suggesting an imbalance between the inflammatory and anti-inflammatory cytokines which is exacerbated by AF. Serum cytokine inflammatory cytokine levels showed that IL-4, IL-5, IL-10, IL-17F, and IL-22 were significant between the AF, AF+CMS, and CMS patients. Combination of both CMS and AF may be associated with a higher degree of inflammation than what is seen in either CMS or AF alone. Thus, the identification of a biomarker capable of identifying metabolic syndrome associated with disease will help in identification of a therapeutic target in treating this devastating disease.
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spelling doaj.art-71e0044102ba460995f171cd80b172662022-12-21T22:47:46ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2020-12-01710.3389/fcvm.2020.613271613271Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic SyndromeHana A. Itani0Hana A. Itani1Miran A. Jaffa2Joseph Elias3Mohammad Sabra4Patrick Zakka5Jad Ballout6Amira Bekdash7Rand Ibrahim8Moustafa Al Hariri9Mirna Ghemrawi10Bernard Abi-Saleh11Maurice Khoury12Samir Alam13Rami Mahfouz14Ayad A. Jaffa15Sami T. Azar16Marwan M. Refaat17Marwan M. Refaat18Faculty of Medicine, American University of Beirut, Beirut, LebanonDepartment of Medicine, Clinical pharmacology, Vanderbilt University Medical Center, Nashville, TN, United StatesEpidemiology and Population Health Department, Faculty of Health Sciences, American University of Beirut, Beirut, LebanonDepartment of Internal Medicine, Cardiology Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonDepartment of Internal Medicine, Cardiology Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonDepartment of Internal Medicine, Emory University Hospital, Atlanta, GA, United StatesDepartment of Internal Medicine, Cardiology Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonFaculty of Medicine, American University of Beirut, Beirut, LebanonDepartment of Internal Medicine, Cardiology Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonDepartment of Emergency Medicine, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonDepartment of Pathology and Laboratory Medicine, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonDepartment of Internal Medicine, Cardiology Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonDepartment of Internal Medicine, Cardiology Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonDepartment of Internal Medicine, Cardiology Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonDepartment of Pathology and Laboratory Medicine, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonDepartment of Biochemistry and Molecular Genetics, American University of Beirut Faculty of Medicine, Beirut, LebanonDepartment of Internal Medicine, Endocrinology Diabetes and Metabolism Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonDepartment of Internal Medicine, Cardiology Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, LebanonDepartment of Biochemistry and Molecular Genetics, American University of Beirut Faculty of Medicine, Beirut, LebanonAtrial fibrillation (AF) and cardiometabolic syndrome (CMS) have been linked to inflammation and fibrosis. However, it is still unknown which inflammatory cytokines contribute to the pathogenesis of AF. Furthermore, cardiometabolic syndrome (CMS) risk factors such as obesity, hypertension, insulin resistance/glucose intolerance are also associated with inflammation and increased level of cytokines and adipokines. We hypothesized that the inflammatory immune response is exacerbated in patients with both AF and CMS compared to either AF or CMS alone. We investigated inflammatory cytokines and fibrotic markers as well as cytokine genetic profiles in patients with lone AF and CMS. CMS, lone AF patients, patients with both lone AF and CMS, and control patients were recruited. Genetic polymorphisms in inflammatory and fibrotic markers were assessed. Serum levels of connective tissue growth factor (CTGF) were tested along with other inflammatory markers including platelet-to-lymphocyte ratio (PLR), monocyte-to-HDL ratio (MHR) in three groups of AF+CMS, AF, and CMS patients. There was a trend in the CTGF levels for statistical significance between the AF and AF+CMS group (P = 0.084). Genotyping showed high percentages of patients in all groups with high secretor genotypes of Interleukin-6 (IL-6) (P = 0.037). Genotyping of IFN-γ and IL-10 at high level showed an increase in expression in the AF + CMS group compared to AF and CMS alone suggesting an imbalance between the inflammatory and anti-inflammatory cytokines which is exacerbated by AF. Serum cytokine inflammatory cytokine levels showed that IL-4, IL-5, IL-10, IL-17F, and IL-22 were significant between the AF, AF+CMS, and CMS patients. Combination of both CMS and AF may be associated with a higher degree of inflammation than what is seen in either CMS or AF alone. Thus, the identification of a biomarker capable of identifying metabolic syndrome associated with disease will help in identification of a therapeutic target in treating this devastating disease.https://www.frontiersin.org/articles/10.3389/fcvm.2020.613271/fullcardiac arrhythmiacardiovascular diseasesheart diseasesatrial fibrillationinflammatory markersmetabolic syndrome
spellingShingle Hana A. Itani
Hana A. Itani
Miran A. Jaffa
Joseph Elias
Mohammad Sabra
Patrick Zakka
Jad Ballout
Amira Bekdash
Rand Ibrahim
Moustafa Al Hariri
Mirna Ghemrawi
Bernard Abi-Saleh
Maurice Khoury
Samir Alam
Rami Mahfouz
Ayad A. Jaffa
Sami T. Azar
Marwan M. Refaat
Marwan M. Refaat
Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic Syndrome
Frontiers in Cardiovascular Medicine
cardiac arrhythmia
cardiovascular diseases
heart diseases
atrial fibrillation
inflammatory markers
metabolic syndrome
title Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic Syndrome
title_full Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic Syndrome
title_fullStr Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic Syndrome
title_full_unstemmed Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic Syndrome
title_short Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic Syndrome
title_sort genomic and proteomic study of the inflammatory pathway in patients with atrial fibrillation and cardiometabolic syndrome
topic cardiac arrhythmia
cardiovascular diseases
heart diseases
atrial fibrillation
inflammatory markers
metabolic syndrome
url https://www.frontiersin.org/articles/10.3389/fcvm.2020.613271/full
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