Plasma FABP4 levels are associated with left atrial fat volume in persistent atrial fibrillation and predict recurrence after catheter ablation

Lopez-Canoa, J N; Baluja, Aurora; Couselo‐Seijas, Marinela; Naveira, Alberto; González‐Melchor, Laila; Rozados, A. Mariño; Martínez‐Sande, Luis; García‐Seara, Javier; Fernández-López, X A; Fernández, Ángel L.; González-Juanàtey, José Ramón; Eiras, Sonia; Rodríguez‐Mañero, Moisés

doi:10.1016/j.ijcard.2019.04.031

Cited by 16 publications

(15 citation statements)

References 36 publications

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“…Our results showed an enhance of lipid accumulation in SAT and EAT SVC. Our previous findings showed an association of both local and peripheral FABP4 (a carrier protein for fatty acids) concentration levels with left atrial adipose tissue volume in persistent but not in paroxysmal AF patients 35 . Additionally, our results confirmed that epicardial stroma has already a higher lipidic profile in permanent AF.…”

Section: Discussionsupporting

confidence: 83%

“…Our previous findings showed an association of both local and peripheral FABP4 (a carrier protein for fatty acids) concentration levels with left atrial adipose tissue volume in persistent but not in paroxysmal AF patients. 35 Additionally, our results confirmed that epicardial stroma has already a higher lipidic profile in permanent AF. Taking all our results together, we get to one hypothesis that goes in line with the findings obtained in murine models by Furuhashi et al 43 In fact, the long-term implication of the cholinergic system in FABP4 regulation was evidenced when these protein levels were sharply decreased in vagus nerve-denervated rats.…”

Section: F I G U R E 5 Neutrophil Migration By Acutesupporting

confidence: 78%

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Inflammatory and lipid regulation by cholinergic activity in epicardial stromal cells from patients who underwent open‐heart surgery

Couselo‐Seijas

Lopez-Canoa

Fernández

et al. 2020

J Cellular Molecular Medi

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The modulation of acetylcholine (ACh) release by botulinum toxin injection into epicardial fat diminishes atrial fibrillation (AF) recurrence. These results suggest an interaction between autonomic imbalance and epicardial fat as risk factors of AF. Our aim was to study the inflammatory, lipidic and fibroblastic profile of epicardial stroma from patients who underwent open‐heart surgery, their regulation by cholinergic activity and its association with AF. We performed in vitro and ex vivo assays from paired subcutaneous and epicardial stromal cells or explants from 33 patients. Acute ACh effects in inflammation and lipid‐related genes were analysed by qPCR, in intracellular calcium mobilization were performed by Fluo‐4 AM staining and in neutrophil migration by trans‐well assays. Chronic ACh effects on lipid accumulation were visualized by AdipoRed. Plasma protein regulation by parasympathetic denervation was studied in vagotomized rats. Our results showed a higher pro‐inflammatory profile in epicardial regarding subcutaneous stromal cells. Acute ACh treatment up‐regulated monocyte chemoattractant protein 1 levels. Chronic ACh treatment improved lipid accumulation within epicardial stromal cells (60.50% [22.82‐85.13] vs 13.85% [6.17‐23.16], P < .001). Additionally, patients with AF had higher levels of fatty acid‐binding protein 4 (1.54 ± 0.01 vs 1.47 ± 0.01, P = .005). Its plasma levels were pronouncedly declined in vagotomized rats (2.02 ± 0.21 ng/mL vs 0.65 ± 0.23 ng/mL, P < .001). Our findings support the characterization of acute or chronic cholinergic activity on epicardial stroma and its association with AF.

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Section: Discussionsupporting

confidence: 83%

Section: F I G U R E 5 Neutrophil Migration By Acutesupporting

confidence: 78%

Inflammatory and lipid regulation by cholinergic activity in epicardial stromal cells from patients who underwent open‐heart surgery

Couselo‐Seijas

Lopez-Canoa

Fernández

et al. 2020

J Cellular Molecular Medi

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“…However, as our study was cross-sectional, we cannot comment on heart failure incidence. A recent publication reported an association between FABP4 and atrial fibrillation [9], however in our study sample the incidence of atrial fibrillation was only about 20% and we did not observe different rates of atrial fibrillation in patients with lower or higher FABP4 levels.…”

Section: Comparisons With the Published Literaturecontrasting

confidence: 95%

“…FABP4 from epicardial fat might have adverse effects on coronary artery disease and atrial fibrillation. [8,9] Also basic research studies have shown that FABP4 suppresses contraction of cardiomyocytes [11] and increase intracellular lipid accumulation in cardiomyocytes [12]. However, even in light of this overwhelming evidence of potential harmful associations, a potential beneficial, dose-dependent association on the myocardium needs further investigation, especially as FABP4-inhibition or FABP4-receptor-blocking have been discussed as possible therapeutic target in the metabolic syndrome [22].…”

Section: Possible Dose-dependent Associationsmentioning

confidence: 99%

The adipokine fatty-acid binding protein 4 and cardiac remodeling

Jeinsen

Ritzen

Vietheer

et al. 2020

Cardiovasc Diabetol

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Background: Previous publications about the association between fatty-acid binding protein 4 (FABP4) and cardiac remodeling have reported different, both beneficial and harmful, associations. Aim of the present investigation was to evaluate the association of FABP4 with parameters of myocardial remodeling defined by cardiac magnetic resonance imaging (CMR). Methods: We investigated plasma FABP4 levels in 331 patients (71% men, mean age 63±13 years) with preserved left ventricular ejection fraction (LVEF ≥ 55%) who underwent a CMR examination. We used linear cox regression to investigate associations between FABP4 and left ventricular end-diastolic diameter (LVEDD), right ventricular enddiastolic diameter (RVEDD), relative wall thickness (RWT), left ventricular mass index (LVMI), and LVEF (unadjusted and adjusted for age, sex, body mass index, cardiac biomarkers, and comorbidities). Results: FABP4 levels were associated with lower LVMI and higher NT-proBNP levels in an adjusted model. The inverse association between FABP4 and LVMI was more pronounced in lower FABP4 levels, whereas the positive association between FABP4 and NT-proBNP was more pronounced in relatively high NT-proBNP levels. Conclusions: Possible beneficial and harmful associations between FABP4 and left ventricular size have been reported. Our results suggest a beneficial association with LVMI (more pronounced in lower FABP4 levels) but a harmful association with NT-proBNP (more pronounced in higher FABP4 levels). Therefore, our results might indicate a potential dose-dependent association of FABP4, but this observation needs further investigation in larger study samples.

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“…Additionally, genes involved in adipogenesis such as Perilipin and Adiponectin (an adipokine secreted adipocyte) (Liao et al, 2005;Ouchi et al, 2011) or metabolism pathways such as transcription factors C/ebp, Ppar are upregulated in obese mouse atria. Finally, transcripts of lipid protein chaperones (FABP) including the adipocyte-type Fabp4 (or ap2), the heart/muscle Fabp3 and the epithelial/epidermal Fabp5, were detected in the atrial myocardium of obese mice (Lopez-Canoa et al, 2019;Shingu et al, 2018Shingu et al, , 2020Umbarawan et al, 2017). The FABPs facilitate the transport of FA to mitochondria (Rodríguez-Calvo et al, 2019) regulated lipid oxidation (Bonen et al, 2009) and storage (Rodríguez-Calvo et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

High Fat Diet Stimulates Beta-Oxidation, Alters Electrical Properties and Induces Adipogenicity of Atria in Obese Mice

Suffee

Baptista

Piquereau

et al. 2020

Preprint

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Metabolic disorders such as obesity are risk factors of atrial fibrillation, not only by sharing comorbidities but likely through their direct impact on atria, notably its adipogenicity. Here, we submitted mice that lack cardiac adipose tissue to a high fat diet and first studied the atrial metabolomic and lipidomic phenotypes using liquid chromatography-mass spectrometry. We found an increased consumption of free fatty acid by the beta-oxidation and an accumulation of long-chain lipids in atria of obese mice. Free fatty acid was the main substrate of mitochondrial respiration studied in the saponin-permeabilized atrial muscle. Conducted action potential recorded in atrial trabeculae was short, and ATP-sensitive potassium current was increased in perforated patch-clamp atrial myocytes of obese mice. There was histological and phenotypical evidence for an accumulation of adipose tissue in obese mice atria. Thus, an obesogenic diet transforms the energy metabolism, causes fat accumulation and induces electrical remodeling of atria myocardium.

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Plasma FABP4 levels are associated with left atrial fat volume in persistent atrial fibrillation and predict recurrence after catheter ablation

Cited by 16 publications

References 36 publications

Inflammatory and lipid regulation by cholinergic activity in epicardial stromal cells from patients who underwent open‐heart surgery

Inflammatory and lipid regulation by cholinergic activity in epicardial stromal cells from patients who underwent open‐heart surgery

The adipokine fatty-acid binding protein 4 and cardiac remodeling

High Fat Diet Stimulates Beta-Oxidation, Alters Electrical Properties and Induces Adipogenicity of Atria in Obese Mice

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