Abstract
BackgroundThis study aimed to evaluate atrium extracellular matrix remodeling in atrial fibrillation (AF) patients with severe aortic stenosis, through histological fibrosis quantification and extracellular matrix gene expression analysis, as well as serum quantification of selected protein targets.MethodsA posthoc analysis of a prospective study was performed in a cohort of aortic stenosis patients. Between 2014 and 2019, 56 patients with severe aortic stenosis submitted to aortic valve replacement surgery in a tertiary hospital were selected.ResultsFibrosis was significantly increased in the AF group when compared to sinus rhythm (SR) patients (p = 0.024). Moreover, cardiomyocyte area was significantly higher in AF patients versus SR patients (p = 0.008). Conversely, collagen III gene expression was increased in AF patients (p = 0.038). TIMP1 was less expressed in the atria of AF patients. MMP16/TIMP4 ratio was significantly decreased in AF patients (p = 0.006). TIMP1 (p = 0.004) and TIMP2 (p = 0.012) were significantly increased in the serum of AF patients. Aortic valve maximum (p = 0.0159) and mean (p = 0.031) gradients demonstrated a negative association with serum TIMP1.ConclusionsAtrial fibrillation patients with severe aortic stenosis present increased atrial fibrosis and collagen type III synthesis, with extracellular matrix remodelling demonstrated by a decrease in the MMP16/TIMP4 ratio, along with an increased serum TIMP1 and TIMP2 proteins.
Highlights
This study aimed to evaluate atrium extracellular matrix remodeling in atrial fibrillation (AF) patients with severe aortic stenosis, through histological fibrosis quantification and extracellular matrix gene expression analy‐ sis, as well as serum quantification of selected protein targets
Evidence suggests atrial remodeling is associated with disease occurrence and progression, which involves specific molecular markers of fibrosis such as Tissue Inhibitor of Metalloproteinase (TIMP) 1, Matrix Metalloproteinase (MMP) 9 and Collagen type 1 Carboxy-terminal Peptide (CICP), with diverse contributions according to different AF subtypes [1]
The present study focused on AF patients with aortic stenosis submitted to valve replacement, which could explain the isolated increase in type III collagen gene expression between patient groups
Summary
This study aimed to evaluate atrium extracellular matrix remodeling in atrial fibrillation (AF) patients with severe aortic stenosis, through histological fibrosis quantification and extracellular matrix gene expression analy‐ sis, as well as serum quantification of selected protein targets. Evidence suggests atrial remodeling is associated with disease occurrence and progression, which involves specific molecular markers of fibrosis such as Tissue Inhibitor of Metalloproteinase (TIMP) 1, Matrix Metalloproteinase (MMP) 9 and Collagen type 1 Carboxy-terminal Peptide (CICP), with diverse contributions according to different AF subtypes [1]. These biomarkers appear to increase with higher arrhythmia burden [1]. Atrium TIMP-4 in AF patients with rheumatic heart disease was lower when compared with Sinus Rhythm (SR) patients, while MMP-2, type I, and type II collagen were increased in the AF group [10]
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