Ichitaro Abe1, Yasushi Teshima1, Hidekazu Kondo1, Haruka Kaku1, Shintaro Kira1, Yuki Ikebe1, Shotaro Saito1, Akira Fukui1, Tetsuji Shinohara1, Kunio Yufu1, Mikiko Nakagawa2, Naoki Hijiya3, Masatsugu Moriyama3, Tatsuo Shimada4, Shinji Miyamoto5, Naohiko Takahashi6. 1. Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan. 2. Medical Education Center, Oita University Faculty of Medicine, Oita, Japan. 3. Department of Molecular Pathology, Oita University Faculty of Medicine, Oita, Japan. 4. Oita Medical Technology School, College of Judo Therapy and Acupuncture-Moxibustion, Oita, Japan. 5. Department of Cardiovascular Surgery, Oita University Faculty of Medicine, Oita, Japan. 6. Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan. Electronic address: takanao@oita-u.ac.jp.
Abstract
BACKGROUND: Epicardial adipose tissue (EAT) is associated with atrial fibrillation (AF), but the underlying mechanisms remain to be fully elucidated. OBJECTIVE: The purpose of this study was to examine, using human left atrial appendage (LAA) samples, the interactive relationship between the EAT profile and atrial myocardial fibrosis through histologic and biochemical analyses. METHODS: LAA samples were obtained from 59 consecutive AF patients during cardiovascular surgery. In histologic analysis, adipose tissue, atrial myocardial fibrosis, EAT fibrosis, macrophage infiltration, and matrix metalloproteinase-2 and hypoxia-inducible factor-1α (Hif-1α) expression were evaluated in LAA sections. In biochemical analysis, proinflammatory/fibrotic proteins in EAT, total collagen in left atrial (LA) myocardium, angiopoietin-like protein-2 (Angptl2)-related proteins in EAT, and proinflammatory/fibrotic proteins in serum were evaluated. RESULTS: Histology revealed that the severity of fibrotic remodeling of EAT was associated with LA myocardial fibrosis. Immunohistochemical and electron microscopic findings revealed that fibrotic remodeling of EAT was associated with infiltration of macrophages and myofibroblasts. Protein concentration analysis demonstrated that the total collagen in the LA myocardium was positively correlated with proinflammatory and profibrotic cytokines/chemokines, including interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-α, vascular endothelial growth factor, and matrix metalloproteinase-2 and matrix metalloproteinase-9 in EAT. The proinflammatory and profibrotic cytokines/chemokines in EAT and the total collagen in the LA were also positively correlated with Angptl2 in EAT. CONCLUSION: Our study demonstrated that fibrotic remodeling and cytokines/chemokines in peri-LA EAT were associated with atrial myocardial fibrosis as a substrate of AF. Our results also suggested that overexpression of Hif-1α and Angptl2 may be involved in these processes.
BACKGROUND: Epicardial adipose tissue (EAT) is associated with atrial fibrillation (AF), but the underlying mechanisms remain to be fully elucidated. OBJECTIVE: The purpose of this study was to examine, using human left atrial appendage (LAA) samples, the interactive relationship between the EAT profile and atrial myocardial fibrosis through histologic and biochemical analyses. METHODS: LAA samples were obtained from 59 consecutive AFpatients during cardiovascular surgery. In histologic analysis, adipose tissue, atrial myocardial fibrosis, EAT fibrosis, macrophage infiltration, and matrix metalloproteinase-2 and hypoxia-inducible factor-1α (Hif-1α) expression were evaluated in LAA sections. In biochemical analysis, proinflammatory/fibrotic proteins in EAT, total collagen in left atrial (LA) myocardium, angiopoietin-like protein-2 (Angptl2)-related proteins in EAT, and proinflammatory/fibrotic proteins in serum were evaluated. RESULTS: Histology revealed that the severity of fibrotic remodeling of EAT was associated with LA myocardial fibrosis. Immunohistochemical and electron microscopic findings revealed that fibrotic remodeling of EAT was associated with infiltration of macrophages and myofibroblasts. Protein concentration analysis demonstrated that the total collagen in the LA myocardium was positively correlated with proinflammatory and profibrotic cytokines/chemokines, including interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-α, vascular endothelial growth factor, and matrix metalloproteinase-2 and matrix metalloproteinase-9 in EAT. The proinflammatory and profibrotic cytokines/chemokines in EAT and the total collagen in the LA were also positively correlated with Angptl2 in EAT. CONCLUSION: Our study demonstrated that fibrotic remodeling and cytokines/chemokines in peri-LA EAT were associated with atrial myocardial fibrosis as a substrate of AF. Our results also suggested that overexpression of Hif-1α and Angptl2 may be involved in these processes.
Authors: Hylton P Gordon; Michael G Katz; Shahood Fazal; Virginia L Gillespie; Anthony S Fargnoli; Sarah M Gubara; Sophia J Madjarova; Jonathan A Cohen Journal: Comp Med Date: 2021-06-03 Impact factor: 0.982