Heart remodeling produced by aortic stenosis promotes cardiomyocyte apoptosis mediated by collagen V imbalance |
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Authors: | Paula Grippa Sant’Ana Sabrina Setembre Batah Patrícia Santos Leão Walcy Rosolia Teodoro Sérgio Luiz Borges de Souza Gustavo Augusto Ferreira Mota Danielle Fernandes Vileigas Vitor Loureiro da Silva Dijon Henrique Salomé de Campos Katashi Okoshi Vera Luiza Capelozzi Antonio Carlos Cicogna Alexandre Todorovic Fabro |
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Institution: | 1. Department of Internal Medicine, Botucatu Medical School, São Paulo State University, Brazil;2. Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Brazil;3. Department of Pathology, Faculty of Medicine, University of São Paulo, Brazil |
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Abstract: | Cardiac remodeling (CR) is a structural change of the heart due to chronic hemodynamic overload related to changes in both myocyte and extracellular matrix (ECM). We investigated that the imbalance of collagen V promotes cardiomyocyte apoptosis that contributes to heart failure and cell death. Aortic stenosis was induced surgically and male Wistar rats were randomized to 18 weeks (Sham 18?w, n?=?12; AoS 18?w, n?=?12) and severe of heart failure (Sham HF, n?=?12; AoS HF, n?=?12) groups. Functional and structural echocardiogram, immunohistochemistry for Ki-67, TUNEL assay and Immunofluorescence for collagen were performed. Our main results were: (1) Progressive reduction of cardiac functional capacity due to cardiac remodeling with decreased eject fraction in heart failure; (2) Imbalance of collagen deposition with increased, crowded and irregular collagen I in situ expression; (3) Dysregulation of dynamic control of collagen fibers with exposed epitopes of collagen V; (4) Additional apoptosis that are dependent to cardiac injury. The collagen V expression in cardiac remodeling is for the first time described and may be related to additional apoptosis and autoimmune response. Our findings suggest a critical role of collagen V in cardiac remodeling to modulate and promote heart failure and death. |
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Keywords: | Aortic stenosis Cardiac remodeling Apoptosis Collagen V |
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