Epicardial Adipose Tissue Extracellular Vesicles in Cardiovascular Diseases: History
Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor: , , ,

Epicardial adipose tissue (EAT) is a specialized fat depot that surrounds the heart, in direct contact with the myocardium. EAT is found between the visceral pericardium and the myocardium, with which it shares a bloodstream, EAT being circulation-dependent on the branches of the coronary arteries. The localization of EAT in the heart is distributed between the right ventricle, the anterior wall of the left ventricle, the atrioventricular groove, and the great coronary vessels, reaching the main thickness at the anterior and lateral walls of the right atrium. In physiological conditions, the EAT abundance depends on genetic, epigenetic, and environmental factors, such as pollution, aging, microbiota, and excessive caloric intake. The EAT mass can comprise up to 80% of the heart surface, contributing 20% to its whole mass.

  • epicardial adipose tissue
  • adipose tissue
  • inflammation
  • cardiovascular diseases
  • extracellular vesicles

1. Introduction

For decades, adipose tissue (AT) was not deeply researched, as it was thought to be merely an energy storage depot. The secretory function of AT was only recognized in the mid-1980s, and an increasing number of scientific works involving adipocytes and AT have been published since then. Currently, AT is accepted as the largest endocrine organ, secreting over 600 proteins [1][2]. To date, numerous adipocyte-derived secreted hormones (leptin, adiponectin, and resistin) and effectors have been demonstrated to modulate a plethora of physiological and pathological metabolic processes, spanning from food intake, gluconeogenesis, glucose uptake, fatty-acid oxidation and insulin resistance, to reproductive axes and immune responses.
Cardiovascular diseases (CVDs) are a group of disorders altering heart functionality, which are characterized by a high fatality rate, and are the driving cause of premature death in humans. Among the main risk factors leading to the onset of CVDs are obesity and diabetes [3][4][5]. These pathologies are associated with a low-grade inflammatory state that differentially affects the homeostasis and the secretome of specific AT depots. This leads to an alteration in the release of extracellular vesicles (EVs) in terms of both number and cargo, which is strictly dependent on the type and state of the cellular and tissue origin [6][7]. The role of epicardial adipose tissue (EAT) in this framework is of particular interest, as it has a significantly different transcriptome and secretome compared to other fat depots, and is in direct contact with the heart muscle [8].

2. Epicardial Adipose Tissue Cellular Components

The cellular components of EAT include copies of white adipocytes, which are smaller than those of VAT, and are specialized in energy storage [9], stroma-vascular cells, neurons, and immune cells including lymphocytes (CD3+), macrophages (CD68+), and mast cells [10]. As an adipose depot, EAT is characterized by a secretory activity that, in physiological conditions, ensures myocardium health [11][12].
The direct interaction of EAT with the myocardium, due to the total absence of fascia between the two tissues and their shared microcirculation, favors the vasocrine and paracrine secretions, with these being of particular importance in explaining the role that EAT plays in the development of cardiovascular pathophysiology. Several studies have demonstrated that a dysfunctional EAT mass expansion, together with its pro-inflammatory state and secretome, is associated with coronary artery diseases (CAD) [13], metabolic syndrome [14], chronic heart failure [15][16], and atrial fibrillation (AF) [17][18][19].

3. Epicardial Adipose Tissue Functions

EAT performs many different functions. Due to its elasticity and compressibility, it confers onto the coronary artery a mechanical protection against excessive distortion and compression induced by myocardial contractions [20]. Thanks to the similarity to brown adipose tissue (BAT) and to the molecular features of beige adipocytes, EAT can defend the myocardium against hypothermia and unfavorable hemodynamic conditions, contributing to cardiac cryoprotection [21][22][23]. Moreover, EAT serves as an energy reservoir for the myocardium, having a high capability for mobilization, deposition, and synthesis of free fatty acids (FFAs) [24]. It performs a pivotal function in lipid and glucose homeostasis regulation [25], and pro-inflammatory and anti-inflammatory cytokine production, showing a unique expression profile for genes linked to coagulation, endothelial function, apoptosis, immune response, and a specific secretome [25][26][27][28].

4. Extracellular Vesicles

EVs are membrane-packed vesicles that can be secreted by many mammalian cell types, and can be found in almost all body fluids, including plasma, saliva, and even breast milk. EVs can be divided into two large subgroups, depending on their dimensions and specific membrane markers. The microvesicles (or ectosomes), ranging from 100 nm to 1000 nm, are positive for CD40 ligand, and Annexin A1 or Annexin V [29][30][31]. The smallest EVs, exosomes, ranging from 40 nm to 100 nm, show increased levels of CD63, CD9, and CD81, among others, along with proteins involved in their biogenesis (e.g., Alix, TSG101, FLOT-1) [32]. The biogenesis of these two classes of vesicles is profoundly different, because larger vesicles are generated by the external budding of the plasma membrane, while exosomes are generated in a multistep process, by inward budding of the endocytic cisternae membrane. Firstly, exosome precursors are accumulated in the cytoplasm into multivesicular bodies (MVBs) that, upon proper stimulation, fuse with the plasma membrane, and release mature exosomes in the extracellular space. The cargo of EVs is enriched in proteins, lipids, and various RNAs (mRNA, miRNA, and circular RNA) that are peculiar for parental cells, and for the developmental and functional state of the generating cells. Once in the extracellular fluids, vesicles are internalized into neighboring or even distant target cells by different mechanisms, and upon content release into the intracellular space, their regulatory effects are exerted. However, it is worth considering that, although many studies are aimed at the identification of the exact content of EVs [33][34], a complete understanding of the intricate biological effects and functionality transferred to recipient cells by the EV cargo has still not been reached. An aberrant production and/or cargo of EVs has been established in the context of many different pathological scenarios, including cancer, diabetes, insulin resistance, and CVDs [35][36][37].
Thus, a multitude of different vesicles are present in extracellular space and in body fluids; however, to date, although several separation methods based on an EV’s specific features have been developed, only a mixed EV population can be isolated.

5. Epicardial Adipose Tissue EVs in Cardiovascular Diseases

The inflammatory conditions that characterize different pathologies such as obesity and diabetes are responsible for the fibrotic and inflammatory state of the heart [38][39]. Recently, the epicardial fatty depot has been considered as an important regulator of cardiovascular health status, and its pathological phenotype has been associated with the onset and exacerbation of CVDs [8][19]. As evidence of this, the worsening of coronary atherosclerosis disease (CAD) has been shown to be significantly associated with a reduced adiponectin mRNA level, and with an increased IL-6 mRNA level in EAT [40]. EAT thickness has been correlated with insulin resistance and many other risk factors of cardiovascular pathologies [41][42][43], but the exact mechanism linking EAT to cardiac dysfunction has yet to be fully elucidated. Lately, the role of the EAT secretome, particularly of EVs released by the depot, in the pathogenesis of CVD, has been greatly explored. From the latest studies published in the literature, the hypothesis has been established of a unique secretome characterizing pathological EAT that is involved in the development and propagation of CVD.
Exosomal miRNA-802-5p released by hypertrophic 3T3-L1 cells has been demonstrated to cause insulin resistance in neonatal rat ventricular myocytes through the reduction in the expression of intracellular HSP60, a mitochondrial chaperone already known to be involved in CVDs among obese and diabetic patients [44]. Insulin resistance has been considered the main factor linking the diabetic conditions to the occurrence of many CVDs and heart failure. The close anatomic proximity between the EAT and the myocardium could be the basis of the paracrine crosstalk between the two tissues, explaining a possible mechanism through which EAT impairs insulin signaling, and consequently induces the structural and functional alteration in cardiomyocytes. Moreover, in CAD patients, the EAT microenvironment plays a pivotal role in modulating the cargo of EAT exosomes that in turn is responsible for an impaired adipogenic differentiation in stem cells lying in the depot [45]. Indeed, although epicardial adipose stem cells (EASCs) from CAD and non-CAD patients have an identical adipogenic potential, Wankei Y. et al. have recently demonstrated that it decreases significantly after exposure to EAT-derived exosomes of CAD subjects. This evidence indicates that various factors triggering CAD (e.g., insulin resistance and inflammation) are responsible for an alteration in the EAT secretome. In particular, the effects observed were ascribed to the down-regulation of Neuronatin protein targeted by miR-3064-5p, enriched in EAT-exosomes of CAD patients.
In addition, a direct role of EVs released by EAT in AF onset and propagation was demonstrated for the first time, in a very comprehensive study by Shaihov-Teper et al. [46]. AF is a multifactorial atrial arrhythmia, very often interconnected with CVD. Histological examinations of EAT explant from AF and non-AF patients were analyzed, and an excess of extracellular matrix deposition, and inflammatory cell infiltrations, were found in AF patients. The EVs isolated from EAT explant cultured in vitro have revealed that the vesicles from AF (AF-EVs) were enriched in pro-inflammatory cytokines (IL-6, IL-1a, TNF-α, IL-4), with lower levels of IL-10 (anti-inflammatory and pro-fibrotic cytokine), VEGF and soluble VEGF receptor. The proteomic profile of AF-EVs corroborated the pro-inflammatory and pro-fibrotic outline that may be ascribed to the upregulation of miR-146b, and to a reduction in miR-133a and miRNA-29a expression. Furthermore, the pro-arrhythmic feature of AF-EVs in a two-dimensional hiPSC-derived cardiac cell sheet was demonstrated. Remarkably, the AF-EV profile was independent from the method used for isolation; both ultracentrifugation and size exclusion chromatography isolation preserve the EV signature. Other possible EAT-EVs-dependent pathways implicated in AF pathogenesis involve circular RNAs. Circular RNAs are non-coding RNAs characterized by a closed-loop structure that provides a high stability released in the extracellular space within exosomes [47][48]. They regulate gene expression, acting as sponges by buffering specific miRNA, and impeding their target gene’s silencing [47][49][50]. Recently, the circular RNAs from the EAT of patients with AF were profiled, and an unique expression profile was shown [51]. The reconstruction of a circular RNA–miRNA–mRNA interactional network has demonstrated that hsa_circRNA_000932 and hsa_circRNA_0078619 modulate the expression of many genes involved in the CVD frame, through the interaction with various miRNAs such as miR-103a-2-5p and miR-199a-5p, providing a direct link between EAT exosomal circular RNA, and the structural and functional remodeling of the heart in AF development.
The contribution of the secretome deriving from EAT and AT in inflammatory processes and in the onset of CVDs are summarized in Table 1.
Table 1. The adipose tissue (AT) and epicardial adipose tissue (EAT) secretomes contribute to inflammation and CVD occurrence.
Tissue Effects Mediators Ref
AT insulin resistance and macrophage activation IL-6;
M1 polarization and formation of macrophage foam cells IL-6;
Adipogenesis miR-450a-5p [54]
macrophages M2/M1 phenotypic switching and insulin resistance TNF-α;
secretion of extracellular matrix protein plasminogen activator;
type VI collagen
angiogenesis VEGF;
cell cycle and apoptosis regulation hsa-miR-222-5p;
EAT insulin resistance miR-802-5p [44]
arterial damage adiponectin;
adipogenic differentiation miR-3064-5p [45]
inflammation, fibrosis, and apoptosis promotion IL-1α;
Modulation of inflammation and cell proliferation hsa_circ_0099634; hsa_circ_0000932;
hsa_circ_0097669; hsa_circ_0135289;
hsa_circ_0098155; hsa_circ_0079672

This entry is adapted from the peer-reviewed paper 10.3390/biomedicines11061653


  1. Halberg, N.; Wernstedt-Asterholm, I.; Scherer, P.E. The adipocyte as an endocrine cell. Endocrinol. Metab. Clin. N. Am. 2008, 37, 753–768.
  2. Lehr, S.; Hartwig, S.; Lamers, D.; Famulla, S.; Müller, S.; Hanisch, F.G.; Cuvelier, C.; Ruige, J.; Eckardt, K.; Ouwens, D.M.; et al. Identification and validation of novel adipokines released from primary human adipocytes. Mol. Cell. Proteom. 2012, 11, M111.010504.
  3. Afshin, A.; Forouzanfar, M.H.; Reitsma, M.B.; Sur, P.; Estep, K.; Lee, A.; Marczak, L.; Mokdad, A.H.; Moradi-Lakeh, M.; Naghavi, M.; et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N. Engl. J. Med. 2017, 377, 13–27.
  4. Group, I.H.S. Hypoglycaemia, cardiovascular disease, and mortality in diabetes: Epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol. 2019, 7, 385–396.
  5. Glovaci, D.; Fan, W.; Wong, N.D. Epidemiology of Diabetes Mellitus and Cardiovascular Disease. Curr. Cardiol. Rep. 2019, 21, 21.
  6. Abu-Shahba, N.; Mahmoud, M.; El-Erian, A.M.; Husseiny, M.I.; Nour-Eldeen, G.; Helwa, I.; Amr, K.; ElHefnawi, M.; Othman, A.I.; Ibrahim, S.A.; et al. Impact of type 2 diabetes mellitus on the immunoregulatory characteristics of adipose tissue-derived mesenchymal stem cells. Int. J. Biochem. Cell. Biol. 2021, 140, 106072.
  7. English, J.; Orofino, J.; Cederquist, C.T.; Paul, I.; Li, H.; Auwerx, J.; Emili, A.; Belkina, A.; Cardamone, D.; Perissi, V. GPS2-mediated regulation of the adipocyte secretome modulates adipose tissue remodeling at the onset of diet-induced obesity. Mol. Metab. 2023, 69, 101682.
  8. Iacobellis, G. Epicardial adipose tissue in contemporary cardiology. Nat. Rev. Cardiol. 2022, 19, 593–606.
  9. Iacobellis, G.; Bianco, A.C. Epicardial adipose tissue: Emerging physiological, pathophysiological and clinical features. Trends Endocrinol. Metab. 2011, 22, 450–457.
  10. Iacobellis, G. Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat. Rev. Endocrinol. 2015, 11, 363–371.
  11. Antonopoulos, A.S.; Antoniades, C. The role of epicardial adipose tissue in cardiac biology: Classic concepts and emerging roles. J. Physiol. 2017, 595, 3907–3917.
  12. Oikonomou, E.K.; Antoniades, C. The role of adipose tissue in cardiovascular health and disease. Nat. Rev. Cardiol. 2019, 16, 83–99.
  13. Greulich, S.; Maxhera, B.; Vandenplas, G.; de Wiza, D.H.; Smiris, K.; Mueller, H.; Heinrichs, J.; Blumensatt, M.; Cuvelier, C.; Akhyari, P.; et al. Secretory products from epicardial adipose tissue of patients with type 2 diabetes mellitus induce cardiomyocyte dysfunction. Circulation 2012, 126, 2324–2334.
  14. Pierdomenico, S.D.; Pierdomenico, A.M.; Cuccurullo, F.; Iacobellis, G. Meta-analysis of the relation of echocardiographic epicardial adipose tissue thickness and the metabolic syndrome. Am. J. Cardiol. 2013, 111, 73–78.
  15. Iacobellis, G.; Zaki, M.C.; Garcia, D.; Willens, H.J. Epicardial fat in atrial fibrillation and heart failure. Horm. Metab. Res. 2014, 46, 587–590.
  16. Packer, M. Epicardial Adipose Tissue May Mediate Deleterious Effects of Obesity and Inflammation on the Myocardium. J. Am. Coll. Cardiol. 2018, 71, 2360–2372.
  17. Lau, D.H.; Schotten, U.; Mahajan, R.; Antic, N.A.; Hatem, S.N.; Pathak, R.K.; Hendriks, J.M.; Kalman, J.M.; Sanders, P. Novel mechanisms in the pathogenesis of atrial fibrillation: Practical applications. Eur. Heart J. 2016, 37, 1573–1581.
  18. Wong, C.X.; Sun, M.T.; Odutayo, A.; Emdin, C.A.; Mahajan, R.; Lau, D.H.; Pathak, R.K.; Wong, D.T.; Selvanayagam, J.B.; Sanders, P.; et al. Associations of Epicardial, Abdominal, and Overall Adiposity With Atrial Fibrillation. Circ. Arrhythm. Electrophysiol. 2016, 9, e004378.
  19. Le Jemtel, T.H.; Samson, R.; Ayinapudi, K.; Singh, T.; Oparil, S. Epicardial Adipose Tissue and Cardiovascular Disease. Curr. Hypertens. Rep. 2019, 21, 36.
  20. Wu, Y.; Zhang, A.; Hamilton, D.J.; Deng, T. Epicardial Fat in the Maintenance of Cardiovascular Health. Methodist. Debakey Cardiovasc. J. 2017, 13, 20–24.
  21. Chechi, K.; Voisine, P.; Mathieu, P.; Laplante, M.; Bonnet, S.; Picard, F.; Joubert, P.; Richard, D. Functional characterization of the Ucp1-associated oxidative phenotype of human epicardial adipose tissue. Sci. Rep. 2017, 7, 15566.
  22. Sacks, H.S.; Fain, J.N.; Bahouth, S.W.; Ojha, S.; Frontini, A.; Budge, H.; Cinti, S.; Symonds, M.E. Adult epicardial fat exhibits beige features. J. Clin. Endocrinol. Metab. 2013, 98, E1448–E1455.
  23. Sacks, H.S.; Fain, J.N.; Holman, B.; Cheema, P.; Chary, A.; Parks, F.; Karas, J.; Optican, R.; Bahouth, S.W.; Garrett, E.; et al. Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: Epicardial fat functioning as brown fat. J. Clin. Endocrinol. Metab. 2009, 94, 3611–3615.
  24. Marchington, J.M.; Pond, C.M. Site-specific properties of pericardial and epicardial adipose tissue: The effects of insulin and high-fat feeding on lipogenesis and the incorporation of fatty acids in vitro. Int. J. Obes. 1990, 14, 1013–1022.
  25. Iacobellis, G.; Barbaro, G. Epicardial adipose tissue feeding and overfeeding the heart. Nutrition 2019, 59, 1–6.
  26. McAninch, E.A.; Fonseca, T.L.; Poggioli, R.; Panos, A.L.; Salerno, T.A.; Deng, Y.; Li, Y.; Bianco, A.C.; Iacobellis, G. Epicardial adipose tissue has a unique transcriptome modified in severe coronary artery disease. Obesity 2015, 23, 1267–1278.
  27. Venteclef, N.; Guglielmi, V.; Balse, E.; Gaborit, B.; Cotillard, A.; Atassi, F.; Amour, J.; Leprince, P.; Dutour, A.; Clément, K.; et al. Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines. Eur. Heart J. 2015, 36, 795a–805a.
  28. Christensen, R.H.; von Scholten, B.J.; Hansen, C.S.; Heywood, S.E.; Rosenmeier, J.B.; Andersen, U.B.; Hovind, P.; Reinhard, H.; Parving, H.H.; Pedersen, B.K.; et al. Epicardial, pericardial and total cardiac fat and cardiovascular disease in type 2 diabetic patients with elevated urinary albumin excretion rate. Eur. J. Prev. Cardiol. 2017, 24, 1517–1524.
  29. Mobarrez, F.; Sjövik, C.; Soop, A.; Hållström, L.; Frostell, C.; Pisetsky, D.S.; Wallén, H. CD40L expression in plasma of volunteers following LPS administration: A comparison between assay of CD40L on platelet microvesicles and soluble CD40L. Platelets 2015, 26, 486–490.
  30. Jeppesen, D.K.; Fenix, A.M.; Franklin, J.L.; Higginbotham, J.N.; Zhang, Q.; Zimmerman, L.J.; Liebler, D.C.; Ping, J.; Liu, Q.; Evans, R.; et al. Reassessment of Exosome Composition. Cell 2019, 177, 428–445.e18.
  31. Crowley, L.C.; Marfell, B.J.; Scott, A.P.; Waterhouse, N.J. Quantitation of Apoptosis and Necrosis by Annexin V Binding, Propidium Iodide Uptake, and Flow Cytometry. Cold Spring Harb. Protoc. 2016, 2016, pdb-prot087288.
  32. Théry, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 2018, 7, 1535750.
  33. Luo, T.; Chen, S.Y.; Qiu, Z.X.; Miao, Y.R.; Ding, Y.; Pan, X.Y.; Li, Y.; Lei, Q.; Guo, A.Y. Transcriptomic Features in a Single Extracellular Vesicle via Single-Cell RNA Sequencing. Small Methods 2022, 6, e2200881.
  34. Zanotti, F.; Zanolla, I.; Trentini, M.; Tiengo, E.; Pusceddu, T.; Licastro, D.; Degasperi, M.; Leo, S.; Tremoli, E.; Ferroni, L.; et al. Mitochondrial Metabolism and EV Cargo of Endothelial Cells Is Affected in Presence of EVs Derived from MSCs on Which HIF Is Activated. Int. J. Mol. Sci. 2023, 24, 2.
  35. Groot, M.; Lee, H. Sorting Mechanisms for MicroRNAs into Extracellular Vesicles and Their Associated Diseases. Cells 2020, 9, 1044.
  36. Gardin, C.; Ferroni, L.; Leo, S.; Tremoli, E.; Zavan, B. Platelet-Derived Exosomes in Atherosclerosis. Int. J. Mol. Sci. 2022, 23, 12546.
  37. Andjus, P.; Kosanović, M.; Milićević, K.; Gautam, M.; Vainio, S.J.; Jagečić, D.; Kozlova, E.N.; Pivoriūnas, A.; Chachques, J.C.; Sakaj, M.; et al. Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage. Int. J. Mol. Sci. 2020, 21, 6859.
  38. Selthofer-Relatić, K.; Bošnjak, I. Myocardial fat as a part of cardiac visceral adipose tissue: Physiological and pathophysiological view. J. Endocrinol. Investig. 2015, 38, 933–939.
  39. Zhou, M.; Wang, H.; Chen, J.; Zhao, L. Epicardial adipose tissue and atrial fibrillation: Possible mechanisms, potential therapies, and future directions. Pacing Clin. Electrophysiol. 2020, 43, 133–145.
  40. Eiras, S.; Teijeira-Fernández, E.; Shamagian, L.G.; Fernandez, A.L.; Vazquez-Boquete, A.; Gonzalez-Juanatey, J.R. Extension of coronary artery disease is associated with increased IL-6 and decreased adiponectin gene expression in epicardial adipose tissue. Cytokine 2008, 43, 174–180.
  41. Hruskova, J.; Maugeri, A.; Podroužková, H.; Štípalová, T.; Jakubík, J.; Barchitta, M.; Medina-Inojosa, J.R.; Homolka, M.; Agodi, A.; Kunzova, S.; et al. Association of Cardiovascular Health with Epicardial Adipose Tissue and Intima Media Thickness: The Kardiovize Study. J. Clin. Med. 2018, 7, 113.
  42. Iacobellis, G.; Ribaudo, M.C.; Assael, F.; Vecci, E.; Tiberti, C.; Zappaterreno, A.; Di Mario, U.; Leonetti, F. Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: A new indicator of cardiovascular risk. J. Clin. Endocrinol. Metab. 2003, 88, 5163–5168.
  43. Monti, C.B.; Codari, M.; De Cecco, C.N.; Secchi, F.; Sardanelli, F.; Stillman, A.E. Novel imaging biomarkers: Epicardial adipose tissue evaluation. Br. J. Radiol. 2020, 93, 20190770.
  44. Wen, Z.; Li, J.; Fu, Y.; Zheng, Y.; Ma, M.; Wang, C. Hypertrophic Adipocyte-Derived Exosomal miR-802-5p Contributes to Insulin Resistance in Cardiac Myocytes Through Targeting HSP60. Obesity 2020, 28, 1932–1940.
  45. Yang, W.; Tu, H.; Tang, K.; Huang, H.; Ou, S.; Wu, J. MiR-3064 in Epicardial Adipose-Derived Exosomes Targets Neuronatin to Regulate Adipogenic Differentiation of Epicardial Adipose Stem Cells. Front. Cardiovasc. Med. 2021, 8, 709079.
  46. Shaihov-Teper, O.; Ram, E.; Ballan, N.; Brzezinski, R.Y.; Naftali-Shani, N.; Masoud, R.; Ziv, T.; Lewis, N.; Schary, Y.; Levin-Kotler, L.P.; et al. Extracellular Vesicles from Epicardial Fat Facilitate Atrial Fibrillation. Circulation 2021, 143, 2475–2493.
  47. Wang, Y.; Liu, J.; Ma, J.; Sun, T.; Zhou, Q.; Wang, W.; Wang, G.; Wu, P.; Wang, H.; Jiang, L.; et al. Exosomal circRNAs: Biogenesis, effect and application in human diseases. Mol. Cancer 2019, 18, 116.
  48. Fanale, D.; Taverna, S.; Russo, A.; Bazan, V. Circular RNA in Exosomes. Adv. Exp. Med. Biol. 2018, 1087, 109–117.
  49. Kristensen, L.S.; Andersen, M.S.; Stagsted, L.V.W.; Ebbesen, K.K.; Hansen, T.B.; Kjems, J. The biogenesis, biology and characterization of circular RNAs. Nat. Rev. Genet. 2019, 20, 675–691.
  50. Tang, Y.; Bao, J.; Hu, J.; Liu, L.; Xu, D.Y. Circular RNA in cardiovascular disease: Expression, mechanisms and clinical prospects. J. Cell. Mol. Med. 2021, 25, 1817–1824.
  51. Zheng, H.; Peng, Y.; Wang, P.; Su, P.; Zhao, L. The integrative network of circRNA, miRNA and mRNA of epicardial adipose tissue in patients with atrial fibrillation. Am. J. Transl. Res. 2022, 14, 6550–6562.
  52. Deng, Z.B.; Poliakov, A.; Hardy, R.W.; Clements, R.; Liu, C.; Liu, Y.; Wang, J.; Xiang, X.; Zhang, S.; Zhuang, X.; et al. Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes 2009, 58, 2498–2505.
  53. Xie, Z.; Wang, X.; Liu, X.; Du, H.; Sun, C.; Shao, X.; Tian, J.; Gu, X.; Wang, H.; Yu, B. Adipose-Derived Exosomes Exert Proatherogenic Effects by Regulating Macrophage Foam Cell Formation and Polarization. J. Am. Heart Assoc. 2018, 7, e007442.
  54. Zhang, Y.; Yu, M.; Dai, M.; Chen, C.; Tang, Q.; Jing, W.; Wang, H.; Tian, W. miR-450a-5p within rat adipose tissue exosome-like vesicles promotes adipogenic differentiation by targeting WISP2. J. Cell Sci. 2017, 130, 1158–1168.
  55. Lumeng, C.N.; Bodzin, J.L.; Saltiel, A.R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Investig. 2007, 117, 175–184.
  56. Lumeng, C.N.; Deyoung, S.M.; Bodzin, J.L.; Saltiel, A.R. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 2007, 56, 16–23.
  57. Castoldi, A.; Naffah de Souza, C.; Câmara, N.O.; Moraes-Vieira, P.M. The Macrophage Switch in Obesity Development. Front. Immunol. 2015, 6, 637.
  58. Jones, P.A.; Scott-Burden, T. Activated macrophages digest the extracellular matrix proteins produced by cultured cells. Biochem. Biophys. Res. Commun. 1979, 86, 71–77.
  59. Schnoor, M.; Cullen, P.; Lorkowski, J.; Stolle, K.; Robenek, H.; Troyer, D.; Rauterberg, J.; Lorkowski, S. Production of type VI collagen by human macrophages: A new dimension in macrophage functional heterogeneity. J. Immunol. 2008, 180, 5707–5719.
  60. Cho, C.H.; Koh, Y.J.; Han, J.; Sung, H.K.; Jong Lee, H.; Morisada, T.; Schwendener, R.A.; Brekken, R.A.; Kang, G.; Oike, Y.; et al. Angiogenic role of LYVE-1-positive macrophages in adipose tissue. Circ. Res. 2007, 100, e47–e57.
  61. An, Y.; Lin, S.; Tan, X.; Zhu, S.; Nie, F.; Zhen, Y.; Gu, L.; Zhang, C.; Wang, B.; Wei, W.; et al. Exosomes from adipose-derived stem cells and application to skin wound healing. Cell Prolif. 2021, 54, e12993.
  62. Eirin, A.; Meng, Y.; Zhu, X.Y.; Li, Y.; Saadiq, I.M.; Jordan, K.L.; Tang, H.; Lerman, A.; van Wijnen, A.J.; Lerman, L.O. The Micro-RNA Cargo of Extracellular Vesicles Released by Human Adipose Tissue-Derived Mesenchymal Stem Cells Is Modified by Obesity. Front. Cell Dev. Biol. 2021, 9, 660851.
  63. Togliatto, G.; Dentelli, P.; Gili, M.; Gallo, S.; Deregibus, C.; Biglieri, E.; Iavello, A.; Santini, E.; Rossi, C.; Solini, A.; et al. Obesity reduces the pro-angiogenic potential of adipose tissue stem cell-derived extracellular vesicles (EVs) by impairing miR-126 content: Impact on clinical applications. Int. J. Obes. 2016, 40, 102–111.
  64. Gan, L.; Xie, D.; Liu, J.; Bond Lau, W.; Christopher, T.A.; Lopez, B.; Zhang, L.; Gao, E.; Koch, W.; Ma, X.L.; et al. Small Extracellular Microvesicles Mediated Pathological Communications Between Dysfunctional Adipocytes and Cardiomyocytes as a Novel Mechanism Exacerbating Ischemia/Reperfusion Injury in Diabetic Mice. Circulation 2020, 141, 968–983.
This entry is offline, you can click here to edit this entry!
Video Production Service