人心外膜脂肪组织通过分泌脂肪成纤维细胞因子诱导心房心肌纤维化。

Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines.

机构信息

Institute of Cardiometabolism and Nutrition, Paris, France INSERM, UMR_S 872, Team 7 Nutriomique, Paris, France Université Pierre et Marie Curie-Paris 6, Cordeliers Research Center, Paris, France.

Institute of Cardiometabolism and Nutrition, Paris, France Université Pierre et Marie Curie-Paris 6, Cordeliers Research Center, Paris, France Université Pierre et Marie Curie-Paris 6, INSERM UMR_S956, Paris, France.

出版信息

Eur Heart J. 2015 Apr 1;36(13):795-805a. doi: 10.1093/eurheartj/eht099. Epub 2013 Mar 22.

DOI:10.1093/eurheartj/eht099

PMID:23525094

Abstract

AIMS

Recent studies have reported a relationship between the abundance of epicardial adipose tissue (EAT) and the risk of cardiovascular diseases including atrial fibrillation (AF). However, the underlying mechanisms are unknown. The aim of this study was to examine the effects of the secretome of human EAT on the histological properties of the myocardium.

METHODS AND RESULTS

Samples of EAT and subcutaneous adipose (SAT), obtained from 39 patients undergoing coronary bypass surgery, were analysed and tested in an organo-culture model of rat atria to evaluate the fibrotic properties of human fat depots. The EAT secretome induced global fibrosis (interstitial and peripheral) of rat atria in organo-culture conditions. Activin A was highly expressed in EAT compared with SAT and promoted atrial fibrosis, an effect blocked using neutralizing antibody. In addition, Activin A levels were enhanced in patients with low left-ventricular function. In sections of human atrial and ventricular myocardium, adipose and myocardial tissues were in close contact, together with fibrosis.

CONCLUSION

This study provides the first evidence that the secretome from EAT promotes myocardial fibrosis through the secretion of adipo-fibrokines such as Activin A.

摘要

目的

最近的研究报告称，心外膜脂肪组织（EAT）的丰度与包括心房颤动（AF）在内的心血管疾病的风险之间存在关系。然而，其潜在机制尚不清楚。本研究旨在研究人 EAT 的分泌组对心肌组织学特性的影响。

方法和结果

从 39 例行冠状动脉搭桥手术的患者中获得 EAT 和皮下脂肪（SAT）样本，并在大鼠心房器官培养模型中进行分析和测试，以评估人脂肪沉积的纤维化特性。EAT 分泌组在器官培养条件下诱导大鼠心房的整体纤维化（间质和周边）。与 SAT 相比，EAT 中激活素 A 的表达水平较高，并促进心房纤维化，而中和抗体可阻断该作用。此外，在左心室功能低下的患者中，激活素 A 的水平增强。在人心房和心室心肌组织的切片中，脂肪组织和心肌组织紧密接触，并伴有纤维化。