Abstract 14422: Epicardial Fat Tissue Causes the Fibrosis of Rat Atrial Myocardium via the Secretion of Activin A
A relationship between the thickness of epicardial adipose tissue (EAT) and the incidence and severity of atrial fibrillation (AF) has been reported. One hypothesis is that EAT secretes molecules that can contribute to the formation of the AF substrate. To test this hypothesis, samples of EAT and subcutaneous adipose tissue (SAT) were obtained from 39 patients undergoing coronary bypass surgery and samples were then maintained in cultured. The secretome was obtained by harvesting the conditioned culture media. We developed an original organoculture model of rat atria to test the effect of the secretome on the myocardium. Fibrosis was characterized by histological assays and quantified using histomorphometry software. The secretome from EAT but not SAT induced marked atrial fibrosis at day 7 of culture (EAT: 33.78%±1.33 vs. SAT: 15.33%±1.60; P=0.001). In addition, the EAT secretome stimulated the differentiation of cultured atrial fibroblasts into myofibroblasts and the synthesis of collagen types I and VI. Using an enzyme-linked immunosorbent assay, we found that Activin A, a member of the transforming growth factor (TGF) superfamily, was highly expressed in EAT compared with SAT (3-fold) and abundantly secreted by EAT. Treatment of atrial organocultures with Activin A (5 ng/mL) for 7 days caused marked fibrosis (36.36%±2.04 vs. 15.67%±0.78 in controls; P<0.001) an effect blocked using neutralizing Activin A antibodies. In sections of human right atrial appendages, adipose and myocardial tissues were in close contact, together with abundant collagen deposition. This study provides the first evidence that the secretome from EAT can promote atrial fibrosis mediated in part by Activin A. Given the role of fibrosis in the AF substrate this study may explain the relationship between EAT thickness and AF.
- © 2012 by American Heart Association, Inc.