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

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

doi:10.3389/fcvm.2020.613271

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

Front Cardiovasc Med. 2020 Dec 2:7:613271. doi: 10.3389/fcvm.2020.613271. eCollection 2020.

Authors

Hana A Itani^{1

2}, Miran A Jaffa³, Joseph Elias⁴, Mohammad Sabra⁴, Patrick Zakka⁵, Jad Ballout⁴, Amira Bekdash¹, Rand Ibrahim⁴, Moustafa Al Hariri⁶, Mirna Ghemrawi⁷, Bernard Abi-Saleh⁴, Maurice Khoury⁴, Samir Alam⁴, Rami Mahfouz⁷, Ayad A Jaffa⁸, Sami T Azar⁹, Marwan M Refaat^{4

8}

Affiliations

¹ Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
² Department of Medicine, Clinical pharmacology, Vanderbilt University Medical Center, Nashville, TN, United States.
³ Epidemiology and Population Health Department, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon.
⁴ Department of Internal Medicine, Cardiology Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, Lebanon.
⁵ Department of Internal Medicine, Emory University Hospital, Atlanta, GA, United States.
⁶ Department of Emergency Medicine, American University of Beirut Faculty of Medicine and Medical Center, Beirut, Lebanon.
⁷ Department of Pathology and Laboratory Medicine, American University of Beirut Faculty of Medicine and Medical Center, Beirut, Lebanon.
⁸ Department of Biochemistry and Molecular Genetics, American University of Beirut Faculty of Medicine, Beirut, Lebanon.
⁹ Department of Internal Medicine, Endocrinology Diabetes and Metabolism Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, Lebanon.

Abstract

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.

Keywords: atrial fibrillation; cardiac arrhythmia; cardiovascular diseases; gene expression; heart diseases; inflammatory markers; metabolic syndrome.