Adina Elena Stanciu1, Radu Gabriel Vatasescu2, Marcel Marian Stanciu3, Nafija Serdarevic4, Maria Dorobantu2. 1. Institute of Oncology Bucharest, Department of Carcinogenesis and Molecular Biology, 252 Fundeni, 022338 Bucharest, Romania. Electronic address: adinaelenastanciu@yahoo.com. 2. Clinic Emergency Hospital Bucharest, Department of Cardiology, 8 Calea Floreasca, 014461 Bucharest, Romania. 3. University Politehnica of Bucharest, Electrical Engineering Faculty, 313 Splaiul Independentei, 060042 Bucharest, Romania. 4. Institute for Clinical Chemistry and Biochemistry, University of Sarajevo Clinics Center, Bolnicka 25, 71000 Sarajevo, Bosnia and Herzegovina.
Abstract
PURPOSE: Signaling pathways involved in electrical, structural and contractile remodeling processes behind development and progression of atrial fibrillation (AF) have not been completely elucidated, but it seems to be related to complex interactions among neurohormonal and cellular mediators. We aimed to investigate interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-β1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), as biomarkers of atrial remodeling, in patients with paroxysmal and persistent AF, and their correlation with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and left atrial (LA) diameter. METHODS: Thirty-seven patients (22M/15F) with paroxysmal AF, 32 patients (22M/10F) with persistent AF and 30 healthy control subjects (18M/12F) were enrolled in the study. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically. RESULTS: IL-6 levels and MMP-9/TIMP-1 ratio were significantly higher in AF patients than in non-AF controls (P < .001), and in persistent than in paroxysmal AF (P < .001), in line with NT-proBNP and LA diameter. In contrast, TGF-β1levels declined with increasing AF duration (from 51.2 pg/mL, IQR: 38.9-87.9 pg/mL in paroxysmal to 23.9 pg/mL, IQR: 16.9-43.6 pg/mL in persistent AF). TGF-β1 was negatively correlated with NT-proBNP (r = -0.53, P = .001 in paroxysmal AF and r = -0.71, P < .001 in persistent AF) and LA diameter (r = -0.44, P = .006 in paroxysmal AF and r = -0.51, P = .003 in persistent AF). CONCLUSIONS: Our results demonstrate that AF development and progression (from paroxysmal to persistent) is associated with a gradual increase in serum levels of NT-proBNP, IL-6 and MMP-9/TIMP-1 ratio. Moreover, this study suggests that the relationship between TGF-β1, NT-proBNP and LA diameter allows for the progression of atrial remodeling during AF, despite compensatory changes in the TGF-β1 signaling pathway.
PURPOSE: Signaling pathways involved in electrical, structural and contractile remodeling processes behind development and progression of atrial fibrillation (AF) have not been completely elucidated, but it seems to be related to complex interactions among neurohormonal and cellular mediators. We aimed to investigate interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-β1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), as biomarkers of atrial remodeling, in patients with paroxysmal and persistent AF, and their correlation with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and left atrial (LA) diameter. METHODS: Thirty-seven patients (22M/15F) with paroxysmal AF, 32 patients (22M/10F) with persistent AF and 30 healthy control subjects (18M/12F) were enrolled in the study. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically. RESULTS:IL-6 levels and MMP-9/TIMP-1 ratio were significantly higher in AFpatients than in non-AF controls (P < .001), and in persistent than in paroxysmal AF (P < .001), in line with NT-proBNP and LA diameter. In contrast, TGF-β1levels declined with increasing AF duration (from 51.2 pg/mL, IQR: 38.9-87.9 pg/mL in paroxysmal to 23.9 pg/mL, IQR: 16.9-43.6 pg/mL in persistent AF). TGF-β1 was negatively correlated with NT-proBNP (r = -0.53, P = .001 in paroxysmal AF and r = -0.71, P < .001 in persistent AF) and LA diameter (r = -0.44, P = .006 in paroxysmal AF and r = -0.51, P = .003 in persistent AF). CONCLUSIONS: Our results demonstrate that AF development and progression (from paroxysmal to persistent) is associated with a gradual increase in serum levels of NT-proBNP, IL-6 and MMP-9/TIMP-1 ratio. Moreover, this study suggests that the relationship between TGF-β1, NT-proBNP and LA diameter allows for the progression of atrial remodeling during AF, despite compensatory changes in the TGF-β1 signaling pathway.
Authors: Denise M S van Marion; Eva A H Lanters; Kennedy S Ramos; Jin Li; Marit Wiersma; Luciënne Baks-Te Bulte; Agnes J Q M Muskens; Eric Boersma; Natasja M S de Groot; Bianca J J M Brundel Journal: Cells Date: 2020-09-16 Impact factor: 6.600
Authors: Adina E Stanciu; Adina Zamfir-Chiru-Anton; Marcel M Stanciu; Anca Pantea Stoian; Viorel Jinga; Cornelia Nitipir; Alexandru Bucur; Teodora S Pituru; Andreea L Arsene; Cristina M Dragoi; Razvan Hainarosie; Alina C Nicolae; Mirela Gherghe; Dan C Gheorghe; Demetrios A Spandidos; Aristidis Tsatsakis; Maria Papasavva; Nikolaos Drakoulis Journal: Oncol Lett Date: 2019-12-13 Impact factor: 2.967