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

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 followup. 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.

Epicardial adipose tissue in contemporary cardiology

“…By contrast, in HFrEF, this increased activity might increase total catecholamine accumulation in the myocardium and worsen systolic performance. A biopsy study in patients with heart failure showed that, after treatment with isoprenaline (an agonist of the catecholaminergic β-adrenergic receptor), EAT releases molecules involved in the inflammatory response or extracellular matrix 117 . Interestingly, EAT expression of CD5L, a macrophage apoptosis inhibitor stimulated by isoprenaline, was higher in patients with heart failure who developed atrial fibrillation during follow-up, although circulating levels of CD5L were not correlated with the risk of atrial fibrillation 118 .…”

A New Biomarker Tool for Risk Stratification in “de novo” Acute Heart Failure (OROME)

“…In acute HF (AHF), exists a 20–30% of re-hospitalization within the first 3–6 months after discharge. It is coupled with an increase of acute-phase response reactants, measured by C-reactive protein (CRP) or interleukin-6 (IL-6) levels ( Goonewardena et al, 2016 ) and a raise of other several serum inflammatory cytokines levels such as tumor necrosis factor alfa (TNF-α) and interleukin-1b (IL-1β) which are associated with the degree of disease severity, poor outcomes, and mortality ( Goonewardena et al, 2016 ; Agra-Bermejo et al, 2020 ). A number of diagnostic and/or prognostic plasma biomarkers of worsening HF have been proposed during hospitalization and in chronic stable patients.…”

Circulating CD5L is associated with cardiovascular events and all-cause mortality in individuals with chronic kidney disease

“…These findings led to the authors concluding that the inhibition of CD5L could prevent CVD in chronic inflammation and could attenuate the functional impairment after myocardial infarction [ 28 , 29 ]. In humans, higher CD5L concentrations on epicardial fat secretome were found in male subjects with heart failure who developed atrial fibrillation [ 30 ]. Those results also support the hypothesis that CD5L could be useful for predicting CVD.…”