Nicolas Venteclef1, Valeria Guglielmi1, Elise Balse2, Bénédicte Gaborit3, Aurélie Cotillard1, Fabrice Atassi2, Julien Amour4, Pascal Leprince4, Anne Dutour5, Karine Clément6, Stéphane N Hatem7. 1. 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. 2. 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. 3. 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 Heart and metabolism division, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris Faculté de Médecine, INSERM NORT UMR 1062, INRA1260, Aix Marseille Université, Marseille, France. 4. Institute of Cardiometabolism and Nutrition, Paris, France Heart and metabolism division, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris. 5. Faculté de Médecine, INSERM NORT UMR 1062, INRA1260, Aix Marseille Université, Marseille, France. 6. 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 Heart and metabolism division, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris stephane.hatem@upmc.fr karine.clement@psl.aphp.fr. 7. 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 Heart and metabolism division, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris stephane.hatem@upmc.fr karine.clement@psl.aphp.fr.
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. Published on behalf of the European Society of Cardiology. All rights reserved.
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. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Mitsuru Seki; Ryan LaCanna; Jeffery C Powers; Christine Vrakas; Fang Liu; Remus Berretta; Geena Chacko; John Holten; Pooja Jadiya; Tao Wang; Jeffery S Arkles; Joshua M Copper; Steven R Houser; Jianhe Huang; Vickas V Patel; Fabio A Recchia Journal: J Pharmacol Exp Ther Date: 2016-06-27 Impact factor: 4.030