Association of fibrotic remodeling and cytokines/chemokines content in epicardial adipose tissue with atrial myocardial fibrosis in patients with atrial fibrillation

Abe, Ichitaro; Teshima, Yasushi; Kondo, Hidekazu; Kaku, Haruka; Kira, Shintaro; Ikebe, Yuki; Saito, Shotaro; Fukui, Atsushi; Shinohara, Tetsuji; Yufu, Kunio; Nakagawa, Mikiko; Hijiya, Naoki; Moriyama, Masatsugu; Shimada, Toshio; Miyamoto, Shinj̀i; Takahashi, Naohiko

doi:10.1016/j.hrthm.2018.06.025

Cited by 158 publications

(153 citation statements)

References 27 publications

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“…Extracellular fibrosis of EAT has been found in the fatty infiltrate of atrial tissue from AF patients and sheep models of AF [32]. Additionally, fibrosis of perimyocardial EAT has been found to increase in severity concurrently with the extent of atrial fibrosis and the degree of AF [33]. In our study,the non-adipocyte area was not different between the three stratified BMI groups (Figure 3(a)).…”

Section: Adipose Tissue and Adipocyte Size Relationshipsupporting

confidence: 49%

Relationship between epicardial adipose tissue thickness and epicardial adipocyte size with increasing body mass index

et al. 2019

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Macroscopic deposition of epicardial adipose tissue (EAT) has been strongly associated with numerous indices of obesity and cardiovascular disease risk. In contrast, the morphology of EAT adipocytes has rarely been investigated. We aimed to determine whether obesity-driven adipocyte hypertrophy, which is characteristic of other visceral fat depots, is found within EAT adipocytes. EAT samples were collected from cardiac surgery patients (n = 49), stained with haematoxylin & eosin, and analysed for mean adipocyte size and non-adipocyte area. EAT thickness was measured using echocardiography. A significant positive relationship was found between EAT thickness and body mass index (BMI). When stratified into standardized BMI categories, EAT thickness was 58.7% greater (p = 0.003) in patients from the obese (7.3 ± 1.8 mm) compared to normal (4.6 ± 0.9 mm) category. BMI as a continuous variable significantly correlated with EAT thickness (r = 0.56, p < 0.0001). Conversely, no correlation was observed between adipocyte size and either BMI or EAT thickness. No difference in the nonadipocyte area was found between BMI groups. Our results suggest that the increased macroscopic EAT deposition associated with obesity is not caused by adipocyte hypertrophy. Rather, alternative remodelling via adipocyte proliferation might be responsible for the observed EAT expansion. ARTICLE HISTORY

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Section: Adipose Tissue and Adipocyte Size Relationshipsupporting

confidence: 49%

Relationship between epicardial adipose tissue thickness and epicardial adipocyte size with increasing body mass index

et al. 2019

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“…Recent studies have reported a higher volume or thickness of EAT in patients with AF, particularly in those with non-paroxysmal AF [36][37][38] . Some studies have reported a relationship between left atrium size and EAT thickness or volume, which might contribute to atrial brosis or cardiomyocytes electrophysiological disorders leading to AF 10,11,37 . In particular, posterior left atrial adipose tissue is supposed to contribute to the atrial remodeling leading to the onset of AF 39 .…”

Section: Discussionmentioning

confidence: 99%

“…Epicardial adipose tissue (EAT), a metabolically active visceral fat reservoir surrounding and in ltrating myocardium and vessels, is recognized as a source of pro-in ammatory mediators involved in the onset and development of various cardiovascular diseases (CVD), such as coronary artery disease (CAD) and arrhythmias 8,9 . And the increase in EAT volume or thickness is associated with DM and is correlated with left atrial enlargement, atrial brosis, abnormal electrical conduction between cardiomyocytes, and results in the onset of AF 10,11 .…”

Section: Introductionmentioning

confidence: 99%

MiR-21-3p regulation FGFR1/FGF21/PPARγ pathway induces atrial fibrosis by targeting FGFR1 in diabetes

Pan¹,

Lin

et al. 2020

Preprint

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Background: A relationship between the abundance of epicardial adipose tissue (EAT) and the risk of atrial fibrosis and atrial fibrillation (AF) in diabetes mellitus (DM) has been reported. And previous studies have shown that MicroRNA-21 (miR-21) is a regulatory factor in atrial fibrosis and AF. The aim of this study was to examine the role of different subtypes of miR-21 in EAT browning and atrial fibrosis under hyperglycemia conditions.Methods: In vivo, C57BL/6 wild type (WT) and miR-21 knockout (KO) mice were used to establish the diabetic model by intraperitoneal injection of streptozotocin (STZ). In vitro, the EAT adipocytes from miR-21 KO mice were cultured and transfected with miR-21-3p mimic or miR-21-5p mimic and co-cultured with atrial fibroblasts in both HG or LG conditions. The browning of EAT and the fibrosis of fibroblasts were assessed by western blotting, immunofluorescence, Masson staining, and ELISA. The gain- and loss-of-function experiments were used to identified fibroblast growth factor receptor 1 (FGFR1) as the target gene of miR-21-3p.Results: In patients with DM and/or AF, serum hsa-miR-21-3p, instead of hsa-miR-21-5p, was significantly up-regulated. And miR-21 KO clearly ameliorated the atrial fibrosis in the diabetic mice. miR-21-3p as a key regulator that controls EAT browning and participates in atrial fibrosis under hyperglycemia conditions. Moreover, our gain- and loss-of-function experiments showed that FGFR1, as a direct target of miR-21-3p identified a regulatory pathway in EAT adipocytes. Conclusions: MiR-21-3p regulated EAT browning and participated the process of hyperglycemia-induced atrial fibrosis by targeting FGFR1.

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“…EAT is a particular form of visceral fat located between the myocardium and the visceral pericardium and exerts extraordinary endocrine/paracrine functions . EAT alteration towards a proinflammatory and profibrotic course in various pathological stressful conditions can provoke myocardial fibrosis of the LA . Indeed, these effects of EAT on cardiac remodeling are not found in subcutaneous adipose tissue and more pronounced in adjacent regions, that is a local pathogenic effect of EAT, therefore LA remodeling was more affected by peri‐atrial than periventricular, total pericardial, or systemic fat .…”

Section: Discussionmentioning

confidence: 99%

“…Epicardial adipose tissue (EAT), a particular form of visceral fat surrounding the heart has recently been found to be associated with atrial myocardial remodeling via the production of profibrotic cytokines/chemokines and infiltration of various inflammatory cells . Previous studies have demonstrated a positive correlation between EAT and ES as well as AF per se or AF recurrence after CA .…”

Section: Introductionmentioning

confidence: 99%

Association between epicardial adipose tissue and embolic stroke after catheter ablation of atrial fibrillation

Ahn

Shin

Shim

et al. 2019

Cardiovasc electrophysiol

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Introduction Risk factors of embolic stroke (ES) after atrial fibrillation (AF) ablation have not been fully elucidated especially among the Asian subjects, particularly regarding epicardial adipose tissue (EAT) in cardiac imaging. We aimed to assess the incidence of ES during a long‐term follow‐up period after AF ablation and to identify the risk factors associated with postablation ES, specifically focusing on EAT. Methods and Results We enrolled patients who experienced postablation ES and control subjects from a consortium of AF ablation registries from three institutes in Korea. EAT was assessed using multislice computed tomography before AF ablation. A total of 3464 patients who underwent AF ablation were recruited and followed‐up. During a follow‐up of 47.2 ± 36.4 months, ES occurred in 47 patients (1.36%) with a CHA2DS2‐VASc score of 1.48 ± 1.39 and the overall annual incidence of ES was 0.34%. Compared with the control group (n = 190), the ES group showed significantly higher prior thromboembolism (TE) and AF recurrence rates, larger left atrium size, lower creatinine clearance rate (CCr), and greater total and peri‐atrial EAT volume. Multivariate regression analysis demonstrated larger peri‐atrial EAT volume (hazards ratio, 1.065; 95% confidence interval, 1.005‐1.128), in addition to a prior history of TE and lower CCr, was independently associated with postablation ES. When a cut‐off value of peri‐atrial EAT volume of ≥20.15 mL was applied, patients with smaller peri‐atrial EAT volume showed significantly higher ES‐free survival. Conclusion Larger peri‐atrial EAT volume, in addition to prior TE and lower CCr, was independently associated with postablation ES regardless of AF recurrence and CHA2DS2‐VASc score. (ClinicalTrials.gov number, NCT03479073).

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Association of fibrotic remodeling and cytokines/chemokines content in epicardial adipose tissue with atrial myocardial fibrosis in patients with atrial fibrillation

Cited by 158 publications

References 27 publications

Relationship between epicardial adipose tissue thickness and epicardial adipocyte size with increasing body mass index

Relationship between epicardial adipose tissue thickness and epicardial adipocyte size with increasing body mass index

MiR-21-3p regulation FGFR1/FGF21/PPARγ pathway induces atrial fibrosis by targeting FGFR1 in diabetes

Association between epicardial adipose tissue and embolic stroke after catheter ablation of atrial fibrillation

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