CD5L, Macrophage Apoptosis Inhibitor, Was Identified in Epicardial Fat-Secretome and Regulated by Isoproterenol From Patients With Heart Failure

Rosa M Agra-Bermejo; Carla Cacho-Antonio; Adriana Rozados-Luis; Marinela Couselo-Seijas; Angel L Fernandez; J M Martinez-Cereijo; S B Bravo; Jose R Gonzalez-Juanatey; Sonia Eiras

doi:10.3389/fphys.2020.00620

CD5L, Macrophage Apoptosis Inhibitor, Was Identified in Epicardial Fat-Secretome and Regulated by Isoproterenol From Patients With Heart Failure

Front Physiol. 2020 Jun 30:11:620. doi: 10.3389/fphys.2020.00620. eCollection 2020.

Authors

Rosa M Agra-Bermejo^{1

2

3}, Carla Cacho-Antonio^{1

3}, Adriana Rozados-Luis⁴, Marinela Couselo-Seijas⁴, Angel L Fernandez^{3

5}, J M Martinez-Cereijo⁵, S B Bravo⁶, Jose R Gonzalez-Juanatey^{1

2

3}, Sonia Eiras^{3

4}

Affiliations

¹ Cardiology Group, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.
² Cardiovascular Area and Coronary Unit, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
³ CIBERCV, Madrid, Spain.
⁴ Translational Cardiology Group, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.
⁵ Heart Surgery Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
⁶ Proteomic Unit, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.

Abstract

Objectives: Neurohormonal dysfunction, which can regulate epicardial fat activity, is one of the main promoters of atrial fibrillation (AF) in patients with heart failure (HF). Our aim was to study the epicardial fat mediators for AF in patients with HF and its catecholaminergic regulation.

Methods: We have included 29 patients with HF who underwent cardiac surgery and were followed up for 5 years. Released proteins by epicardial adipose tissue (EAT) after isoproterenol treatment were identified by nano-high-performance liquid chromatography (HPLC) and triple time-of-flight (TOF) analysis. Common and differential identified proteins in groups of patients with AF before and after surgery were determined by the FunRich tool. Plasma and epicardial fat biopsy proteins were quantified by western blot.

Results: Our results identified 17 common released proteins by EAT, after isoproterenol treatment, from HF patients who suffered AF or developed new-onset AF during follow-up. Mostly, they were involved on inflammatory response and extracellular matrix. One of them was CD5L, a macrophage apoptosis inhibitor. Its secretion by isoproterenol treatment was validated on western blot. The CD5L levels on epicardial fat were also higher in the group of male patients who present or develop AF (0.44 ± 0.05 vs. 0.18 ± 0.15; p < 0.016). However, there were no differences regarding plasma levels.

Conclusion: Our results suggest the role of epicardial fat CD5L as a mediator of AF and its possible paracrine effect by catecholaminergic activity.

Keywords: atrial fibrillation; epicardial fat; heart failure; inflammation; proteomics.