Heart remodeling produced by aortic stenosis promotes cardiomyocyte apoptosis mediated by collagen V imbalance

• Published in: Pathophysiology (Amsterdam) Vol. 25; no. 4; pp. 373 - 379
• Main Authors: Sant’Ana, Paula Grippa, Batah, Sabrina Setembre, Leão, Patrícia Santos, Teodoro, Walcy Rosolia, de Souza, Sérgio Luiz Borges, Ferreira Mota, Gustavo Augusto, Vileigas, Danielle Fernandes, da Silva, Vitor Loureiro, de Campos, Dijon Henrique Salomé, Okoshi, Katashi, Capelozzi, Vera Luiza, Cicogna, Antonio Carlos, Fabro, Alexandre Todorovic
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2018
• Subjects: Aortic stenosis; Apoptosis; Cardiac remodeling; Collagen V; Aortic stenosis; Cardiac remodeling; Collagen V; Apoptosis
• ISSN: 0928-4680; 1873-149X
• DOI: 10.1016/j.pathophys.2018.07.001

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.