Association of fibrotic remodeling and cytokines/chemokines content in epicardial adipose tissue with atrial myocardial fibrosis in patients with atrial fibrillation
Association of fibrotic remodeling and cytokines/chemokines content in epicardial adipose tissue with atrial myocardial fibrosis in patients with atrial fibrillation
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DOI：
10.1016/j.hrthm.2018.06.025
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发表时间：
2018-11-01
期刊：
影响因子：
5.5
通讯作者：
Takahashi, Naohiko
中科院分区：
文献类型：
--
作者：
Abe, Ichitaro;Teshima, Yasushi;Takahashi, Naohiko
背景心外膜脂肪组织(EAT)与心房颤动(房颤)相关，但其机制尚未完全阐明。目的本研究的目的是通过组织学和生化分析，以人的左心耳(LAA)为样本，研究EAT与心房心肌纤维化之间的相互作用关系。组织学观察左心耳切片脂肪组织、心肌纤维化、EAT纤维化、巨噬细胞浸润及基质金属蛋白酶-2和低氧诱导因子-1α(Hif-1α)的表达。生化分析检测EAT中促炎症/纤维化蛋白、左心房(LA)心肌总胶原、EAT中血管生成素样蛋白-2(Angptl2)相关蛋白及血清中促炎症/纤维蛋白。免疫组织化学和电子显微镜结果显示，EAT纤维化重塑与巨噬细胞和肌成纤维细胞的浸润有关。蛋白浓度分析显示，LA心肌中总胶原与EAT中促炎症和促纤维化的细胞因子/趋化因子呈正相关，包括IL-6、单核细胞趋化蛋白-1、肿瘤坏死因子-α、血管内皮生长因子、基质金属蛋白酶-2和基质金属蛋白酶-9。EAT中促炎症和促纤维化的细胞因子/趋化因子及左房内总胶原与Angptl2呈正相关。结论EAT周围的纤维化重塑和细胞因子/趋化因子与房颤的发生有关。我们的结果还表明，Hif-1α和Angptl2的过度表达可能参与了这些过程。
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-1 alpha (Hif-1 alpha) 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-alpha, 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-1 alpha and Angptl2 may be involved in these processes.