Secretory products from epicardial adipose tissue of patients with type 2 diabetes mellitus induce cardiomyocyte dysfunction
Abstract
BACKGROUND: Secreted factors from epicardial adipose tissue (EAT) have been implicated in the development of cardiomyocyte dysfunction. This study aimed to assess whether alterations in the secretory profile of EAT in patients with type 2 diabetes mellitus (DM2) affect contractile function and insulin action in cardiomyocytes. METHODS AND RESULTS: Contractile function and insulin action were analyzed in primary adult rat cardiomyocytes incubated with conditioned media (CM) generated from explants of EAT biopsies obtained from patients without and with DM2. CM from subcutaneous and pericardial adipose tissue biopsies from the same patients served as the control. Cardiomyocytes treated with CM (EAT) from DM2 patients showed reductions in sarcomere shortening, cytosolic Ca(2+) fluxes, expression of sarcoplasmic endoplasmic reticulum ATPase 2a, and decreased insulin-mediated Akt-Ser473-phosphorylation as compared with CM from the other groups. Profiling of the CM showed that activin A, angiopoietin-2, and CD14 selectively accumulated in CM-EAT-DM2 versus CM-EAT in patients without DM2 and CM from the other fat depots. Accordingly, EAT biopsies from DM2 patients were characterized by clusters of CD14-positive monocytes. Furthermore, SMAD2-phosphorylation, a downstream target of activin A signaling, was elevated in cardiomyocytes treated with CM (EAT) from DM2 patients, and the detrimental effects of CM (EAT) from DM2 patients were partially abolished in cardiomyocytes pretreated with a neutralizing antibody against activin A. Finally, both recombinant activin A and angiopoietin-2 reduced cardiomyocyte contractile function, but only activin A reduced the expression of sarcoplasmic endoplasmic reticulum ATPase 2a. CONCLUSIONS: Collectively, our data implicate DM2-related alterations in the secretory profile of EAT in the pathogenesis of diabetes mellitus-related heart disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cardiomyocytes of rat incubated with conditioned media generated from explants of EAT biopsies performed in T2DM patients became dysfunctional and insulin resistant.
“Such a scenario is strongly suggested by the study of Greulich et al. indicating that cardiomyocytes of rat incubated with conditioned media generated from explants of EAT biopsies performed in T2DM patients became dysfunctional and insulin resistant [92].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [92]
The secretion pattern of EAT is considerably different from SAT and PAT, and in diabetic compared to non-diabetic individuals.
“The study also demonstrated that the secretion pattern of EAT was considerably different from SAT and PAT, and in diabetic compared to non-diabetic individuals.”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [92]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Macrophages, inflammation, and insulin resistance
Olefsky, J. M., & Glass, C. K. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135846 · Cited by 2,733 · see citing works
Human epicardial adipose tissue is a source of inflammatory mediators
Mazurek, T., Zhang, L., Zalewski, A., Mannion, J. D., Diehl, J. T., Arafat, H., Sarov-Blat, L., O’Brien, S., Keiper, E. A., Johnson, A. G., et al. (2003) · Circulation · doi:10.1161/01.cir.0000099542.57313.c5 · Cited by 1,966 · see citing works
Epicardial adipose tissue: Anatomic, biomolecular and clinical relationships with the heart
Iacobellis, G., Corradi, D., & Sharma, A. M. (2005) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio0319 · Cited by 1,015 · see citing works
Human epicardial adipose tissue: A review
Sacks, H. S., & Fain, J. N. (2007) · American Heart Journal · doi:10.1016/j.ahj.2007.03.019 · Cited by 971 · see citing works
Kumar, A., Thota, V., Dee, L., Olson, J., Uretz, E. F., & Parrillo, J. E. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.3.949 · Cited by 790 · see citing works
Extracellular control of TGFβ signalling in vascular development and disease
ten Dijke, P., & Arthur, H. M. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2262 · Cited by 777 · see citing works
Diabetic cardiomyopathy, causes and effects
Boudina, S., & Abel, E. D. (2010) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-010-9131-7 · Cited by 730 · see citing works
Echocardiographic epicardial fat: a review of research and clinical applications
Iacobellis, G., & Willens, H. J. (2009) · Journal of the American Society of Echocardiography · doi:10.1016/j.echo.2009.10.013 · Cited by 700 · see citing works
Adipose Tissue Dysfunction in Obesity
Blüher, M. (2009) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0029-1192044 · Cited by 657 · see citing works
Baker, A. R., da Silva, N. F., Quinn, D. W., Harte, A. L., Pagano, D., Bonser, R. S., Kumar, S., & McTernan, P. G. (2006) · Cardiovascular Diabetology · doi:10.1186/1475-2840-5-1 · Cited by 642 · see citing works
Epicardial fat: properties, function and relationship to obesity
Rabkin, S. W. (2006) · Obesity Reviews · doi:10.1111/j.1467-789x.2006.00293.x · Cited by 453 · see citing works
Iacobellis, G., Pistilli, D., Gucciardo, M., Leonetti, F., Miraldi, F., Brancaccio, G., GALLO, P., & Gioia, C. R. T. D. (2005) · Cytokine · doi:10.1016/j.cyto.2004.11.002 · Cited by 445 · see citing works
Coronary Atherosclerosis Is Associated With Macrophage Polarization in Epicardial Adipose Tissue
Hirata, Y., Tabata, M., Kurobe, H., Motoki, T., Akaike, M., Nishio, C., Higashida, M., Mikasa, H., Nakaya, Y., Takanashi, S., et al. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.01.048 · Cited by 424 · see citing works
Rijzewijk, L. J., van der Meer, R. W., Lamb, H. J., de Jong, H. W. A. M., Lubberink, M., Romijn, J. A., Bax, J. J., Roos, A., Twisk, J. W. R., Heine, R. J., et al. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.04.074 · Cited by 304 · see citing works
The Double Role of Epicardial Adipose Tissue as Pro- and Anti-inflammatory Organ
Iacobellis, G., & Bárbaro, G. (2008) · Hormone and Metabolic Research · doi:10.1055/s-2008-1062724 · Cited by 285 · see citing works
Periasamy, M., Bhupathy, P., & Babu, G. J. (2007) · Cardiovascular Research · doi:10.1093/cvr/cvm056 · Cited by 256 · see citing works
Kremen, J., Dolinkova, M., Krajickova, J., Bláha, J., Anderlová, K., Lacinová, Z., Haluzíková, D., Bošanská, L., Vokurka, M., Svacina, S., et al. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1044 · Cited by 238 · see citing works
Ouwens, D. M., Sell, H., Greulich, S., & Eckel, J. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01141.x · Cited by 235 · see citing works
Chaldakov, G. N., Fiore, M., Stankulov, I. S., Manni, L., Hristova, M. G., Antonelli, A., Ghenev, P., & Aloe, L. (2004) · Progress in brain research · doi:10.1016/s0079-6123(03)46018-4 · Cited by 211 · see citing works
Lamounier-Zepter, V., Look, C., Alvarez, J., Christ, T., Ravens, U., Schunck, W.-H., Ehrhart-Bornstein, M., Bornstein, S. R., & Morano, I. (2009) · Circulation Research · doi:10.1161/circresaha.109.200501 · Cited by 203 · see citing works
Activin A Plays a Critical Role in Proliferation and Differentiation of Human Adipose Progenitors
Zaragosi, L.-E., Wdziekonski, B., Villageois, P., Keophiphath, M., Maumus, M., Tchkonia, T., Bourlier, V., Mohsen-Kanson, T., Ladoux, A., Elabd, C., et al. (2010) · Diabetes · doi:10.2337/db10-0013 · Cited by 184 · see citing works
Elevated Levels of Activin A in Heart Failure
Yndestad, A., Ueland, T., Øie, E., Florholmen, G., Halvorsen, B. L., Attramadal, H., Simonsen, S., Frøland, S. S., Gullestad, L. L., Christensen, G., et al. (2004) · Circulation · doi:10.1161/01.cir.0000120704.97934.41 · Cited by 181 · see citing works
Enhanced Inflammation in Epicardial Fat in Patients With Coronary Artery Disease
Hirata, Y., Kurobe, H., Akaike, M., Chikugo, F., Hori, T., Bando, Y., Nishio, C., Higashida, M., Nakaya, Y., Kitagawa, T., et al. (2011) · International Heart Journal · doi:10.1536/ihj.52.139 · Cited by 173 · see citing works
Karastergiou, K., Evans, I. M., Ogston, N., Miheisi, N., Nair, D. R., Kaski, J. C., Jahangiri, M., & Mohamed‐Ali, V. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.204719 · Cited by 169 · see citing works
Fain, J. N., Sacks, H. S., Buehrer, B. M., Bahouth, S. W., Garrett, E., Wolf, R. Y., Carter, R. A., Tichansky, D. S., & Madan, A. K. (2008) · International Journal of Obesity · doi:10.1038/sj.ijo.0803790 · Cited by 152 · see citing works
Moro, C., Klimčáková, E., Lolmède, K., Berlan, M., Lafontan, M., Štich, V., Bouloumié, A., Galitzky, J., Arner, P., & Langin, D. (2007) · Diabetologia · doi:10.1007/s00125-007-0614-3 · Cited by 133 · see citing works
Role of macrophage tissue infiltration in obesity and insulin resistance
Bourlier, V., & Bouloumié, A. (2009) · Diabetes & Metabolism · doi:10.1016/j.diabet.2009.05.001 · Cited by 132 · see citing works
Maass, D. L., White, J., & Horton, J. W. (2002) · Shock · doi:10.1097/00024382-200210000-00012 · Cited by 126 · see citing works
Lebeche, D., Davidoff, A. J., & Hajjar, R. J. (2008) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio1347 · Cited by 122 · see citing works
Activin A and Follistatin-Like 3 Determine the Susceptibility of Heart to Ischemic Injury
Oshima, Y., Ouchi, N., Shimano, M., Pimentel, D. R., Papanicolaou, K. N., Panse, K. D., Tsuchida, K., Lara‐Pezzi, E., Lee, S., & Walsh, K. (2009) · Circulation · doi:10.1161/circulationaha.109.872200 · Cited by 103 · see citing works
Effects of cytokines on the contractility of cultured cardiac myocytes
Weisensee, D., Bereiter‐Hahn, J., Schoeppe, W., & Löw‐Friedrich, I. (1993) · International Journal of Immunopharmacology · doi:10.1016/0192-0561(93)90075-a · Cited by 95 · see citing works
Vural, B., Atalar, F., Çiftçi, Ç., Demirkan, A., Duman, B. S., Günay, D., Akpınar, B., Sağbaş, E., Özbek, U., & Buyukdevrim, A. S. (2008) · Cardiovascular Pathology · doi:10.1016/j.carpath.2008.02.006 · Cited by 92 · see citing works
Zhou, Y., Wei, Y., Wang, L., Wang, X., Du, X., Sun, Z., Dong, N., & Chen, X. (2011) · Cardiovascular Diabetology · doi:10.1186/1475-2840-10-2 · Cited by 88 · see citing works
Insulin action on the glucose transport system in isolated cardiocytes from adult rat
Eckel, J., Pandalis, G., & Reinauer, H. (1983) · Biochemical Journal · doi:10.1042/bj2120385 · Cited by 81 · see citing works
Epicardial Adipose Tissue Adiponectin Expression is Related to Intracoronary Adiponectin Levels
Iacobellis, G., Gioia, C. R. T. D., Cotesta, D., Petramala, L., Travaglini, C., Santis, V. D., Vitale, D., Tritapepe, L., & Letizia, C. (2008) · Hormone and Metabolic Research · doi:10.1055/s-0028-1100412 · Cited by 81 · see citing works
Greulich, S., de Wiza, D. H., Preilowski, S., Ding, Z., Mueller, H., Langin, D., Jaquet, K., Ouwens, D. M., & Eckel, J. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01232.x · Cited by 70 · see citing works
Clinical and Genetic Correlates of Circulating Angiopoietin-2 and Soluble Tie-2 in the Community
Lieb, W., Zachariah, J. P. V., Xanthakis, V., Safa, R., Chen, M., SULLIVAN, L. M., Larson, M. G., Smith, H., Yang, Q., Mitchell, G. F., et al. (2010) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.109.914556 · Cited by 60 · see citing works
Abe, M., Shintani, Y., Eto, Y., Harada, K., Kosaka, M., & Matsumoto, T. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.2.347 · Cited by 55 · see citing works
Ouwens, D. M., & Diamant, M. (2007) · Archives of Physiology and Biochemistry · doi:10.1080/13813450701422633 · Cited by 41 · see citing works
Andersen, G. Ø., Ueland, T., Knudsen, E. C., Scholz, H., Yndestad, A., Sahraoui, A., Smith, C., Lekva, T., Otterdal, K., Halvorsen, B. L., et al. (2011) · Diabetes · doi:10.2337/db10-1493 · Cited by 33 · see citing works
Explant Cultures of White Adipose Tissue
Thalmann, S., Juge-Aubry, C. E., & Meier, C. A. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-245-8_14 · Cited by 32 · see citing works
Leptin modulates the negative inotropic effect of interleukin-1β in cardiac myocytes
Radin, M. J., Holycross, B. J., Dumitrescu, C., Kelley, R. E., & Altschuld, R. A. (2008) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-008-9805-6 · Cited by 18 · see citing works
Adipocyte-derived factors suppress heart contraction
Look, C., Morano, I. L., Ehrhart‐Bornstein, M., Bornstein, S. R., & Lamounier‐Zepter, V. (2010) · International Journal of Obesity · doi:10.1038/ijo.2010.121 · Cited by 11 · see citing works
Human adipocyte-derived factors directly inhibit cardiac contraction
Look, C., Morano, I. L., & Lamounier‐Zepter, V. (2008) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-009-9172-2 · Cited by 4 · see citing works
[Change of serum soluble CD14 level in newly diagnosed type 2 diabetes and its significance].
Mo, H., Liu, S., Zhou, Z., Tang, W., Yan, X., Huang, G., Li, J., & Feng, Q. (2010) · PubMed · doi:10.3969/j.issn.1672-7347.2010.07.009 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Adipose tissue dysfunction as determinant of obesity-associated metabolic complications
Longo, M., Zatterale, F., Naderi, J., Parrillo, L., Formisano, P., Raciti, G. A., Beguinot, F., & Miele, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092358 · Cited by 1,575 · see citing works
Stærk, L., Sherer, J. A., Ko, D., Benjamin, E. J., & Helm, R. H. (2017) · Circulation Research · doi:10.1161/circresaha.117.309732 · Cited by 1,224 · see citing works
SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control
Cowie, M., & Fisher, M. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-0406-8 · Cited by 805 · see citing works
Local and systemic effects of the multifaceted epicardial adipose tissue depot
Iacobellis, G. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.58 · Cited by 605 · see citing works
Venteclef, N., Guglielmi, V., Balse, E., Gaborit, B., Cotillard, A., Atassi, F., Amour, J., Leprince, P. N., Dutour, A., Clément, K., et al. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht099 · Cited by 594 · see citing works
Diabesity: the combined burden of obesity and diabetes on heart disease and the role of imaging
Ng, A. C. T., Delgado, V., Borlaug, B. A., & Bax, J. J. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-00465-5 · Cited by 339 · see citing works
Fitzgibbons, T. P., & Czech, M. P. (2014) · Journal of the American Heart Association · doi:10.1161/jaha.113.000582 · Cited by 331 · see citing works
Koepp, K. E., Obokata, M., Reddy, Y. N. V., Olson, T. P., & Borlaug, B. A. (2020) · JACC Heart Failure · doi:10.1016/j.jchf.2020.04.016 · Cited by 269 · see citing works
Mechanistic Insights of Empagliflozin in Nondiabetic Patients With HFrEF
Requena-Ibáñez, J. A., Santos‐Gallego, C. G., Rodriguez-Cordero, A., Vargas-Delgado, A. P., MANCINI, D. M., Sartori, S., Atallah-Lajam, F., Giannarelli, C., Macaluso, F., Lala, A., et al. (2021) · JACC Heart Failure · doi:10.1016/j.jchf.2021.04.014 · Cited by 267 · see citing works
Haemers, P., Hamdi, H., Guedj, K., Suffee, N., Farahmand, P., Popović, N., Claus, P., Leprince, P. N., Nicoletti, A., Jalife, J., et al. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv625 · Cited by 260 · see citing works
Epicardial adipose tissue and atrial fibrillation
Hatem, S. N., & Sanders, P. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu045 · Cited by 246 · see citing works
Livshits, G., & Kalinkovich, A. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100980 · Cited by 239 · see citing works
Patel, V. B., Shah, S., Verma, S., & Oudit, G. Y. (2017) · Heart Failure Reviews · doi:10.1007/s10741-017-9644-1 · Cited by 218 · see citing works
Díaz‐Rodriguez, E., Agra, R. M., Fernández, Á. L., Adrio, B., García‐Caballero, T., González‐Juanatey, J. R., & Eiras-Penas, S. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx186 · Cited by 215 · see citing works
The role of epicardial adipose tissue in cardiac biology: classic concepts and emerging roles
Antonopoulos, A. S., & Antoniades, C. A. (2017) · The Journal of Physiology · doi:10.1113/jp273049 · Cited by 197 · see citing works
The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction
Packer, M. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.06.055 · Cited by 190 · see citing works
Antonopoulos, A. S., Margaritis, M., Verheule, S., Récalde, A., Sanna, F., Herdman, L., Psarros, C. T., Nasrallah, H. M., Coutinho, P., Akoumianakis, I., et al. (2016) · Circulation Research · doi:10.1161/circresaha.115.307856 · Cited by 173 · see citing works
Heath, J. M., Sun, Y., Yuan, K., Bradley, W. E., Litovsky, S. H., Dell’Italia, L. J., Chatham, J. C., Wu, H., & Chen, Y. (2014) · Circulation Research · doi:10.1161/circresaha.114.302968 · Cited by 172 · see citing works
Role of Epicardial Adipose Tissue in Health and Disease: A Matter of Fat?
Gaborit, B., Sengenès, C., Ancel, P., Jacquier, A., & Dutour, A. (2017) · Comprehensive physiology · doi:10.1002/cphy.c160034 · Cited by 174 · see citing works
Activin type II receptor signaling in cardiac aging and heart failure
Roh, J. D., Hobson, R., Chaudhari, V., Quintero, P. A., Yeri, A., Benson, M. D., Xiao, C., Zlotoff, D. A., Bezzerides, V. J., Houstis, N. E., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aau8680 · Cited by 148 · see citing works
Pericardial Fat and the Risk of Heart Failure
Kenchaiah, S., Ding, J., Carr, J. J., Allison, M., Budoff, M. J., Tracy, R. P., Burke, G. L., McClelland, R. L., Arai, A. E., & Bluemke, D. A. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.04.003 · Cited by 147 · see citing works
Inflammasome Signaling in Atrial Fibrillation
Ajoolabady, A., Nattel, S., Lip, G. Y. H., & Ren, J. T. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.03.379 · Cited by 148 · see citing works
Ng, A. C. T., Strudwick, M. W., van der Geest, R. J., Ng, A. C. C., Gillinder, L., Goo, S. Y., Cowin, G., Delgado, V., Wang, W. Y. S., & Bax, J. J. (2018) · Circulation Cardiovascular Imaging · doi:10.1161/circimaging.117.007372 · Cited by 140 · see citing works
Packer, M., Lam, C. S. P., Lund, L. H., & Redfield, M. M. (2019) · Circulation · doi:10.1161/circulationaha.119.042996 · Cited by 133 · see citing works
Cardiac adipose tissue and atrial fibrillation: the perils of adiposity
Hatem, S. N., Redheuil, A. B., & Gandjbakhch, E. (2016) · Cardiovascular Research · doi:10.1093/cvr/cvw001 · Cited by 123 · see citing works
Implications of Inflammation and Fibrosis in Atrial Fibrillation Pathophysiology
Harada, M., & Nattel, S. (2021) · Cardiac Electrophysiology Clinics · doi:10.1016/j.ccep.2020.11.002 · Cited by 126 · see citing works
Adipose Tissue: Physiology to Metabolic Dysfunction
Richard, A. J., White, U. A., Elks, C. M., & Stephens, J. M. (2020) · Europe PMC (PubMed Central) · Cited by 118 · see citing works
Greulich, S., Chen, W. J. Y., Maxhera, B., Rijzewijk, L. J., van der Meer, R. W., Jonker, J. T., Mueller, H., de Wiza, D. H., Floerke, R.-R., Smiris, K., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059697 · Cited by 113 · see citing works
Peikert, A., Vaduganathan, M., Claggett, B. L., Kulac, I. J., Litwin, S. E., Zile, M. R., Desai, A. S., Jhund, P. S., Butt, J. H., Lam, C. S. P., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf057 · Cited by 120 · see citing works
Effect of SGLT2-Inhibitors on Epicardial Adipose Tissue: A Meta-Analysis
Masson, W. M., Cobo, A. L., & Nogueira, J. P. (2021) · Cells · doi:10.3390/cells10082150 · Cited by 113 · see citing works
Is epicardial fat depot associated with atrial fibrillation? A systematic review and meta-analysis
Gaeta, M., Bandera, F., Tassinari, F., Capasso, L., Cargnelutti, M., Pelissero, G., Malavazos, A. E., & Ricci, C. (2017) · EP Europace · doi:10.1093/europace/euw398 · Cited by 111 · see citing works
Inflammation in Metabolic Cardiomyopathy
Wenzl, F. A., Ambrosini, S., Mohammed, S. A., Kraler, S. C., Lüscher, T. F., Costantino, S., & Paneni, F. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.742178 · Cited by 109 · see citing works
Mechanisms and Drug Development in Atrial Fibrillation
Calvo, D., Rama, D. F., & Jalife, J. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014183 · Cited by 97 · see citing works
Vacca, M., Eusanio, M. D., Cariello, M., Graziano, G., D’Amore, S., Petridis, F. D., D’Orazio, A., Salvatore, L., Tamburro, A., Folesani, G., et al. (2015) · Cardiovascular Research · doi:10.1093/cvr/cvv266 · Cited by 99 · see citing works
Epicardial adipose tissue feeding and overfeeding the heart
Iacobellis, G., & Barbaro, G. (2019) · Nutrition · doi:10.1016/j.nut.2018.07.002 · Cited by 82 · see citing works
Epicardial adipose tissue in endocrine and metabolic diseases
Iacobellis, G. (2013) · Endocrine · doi:10.1007/s12020-013-0099-4 · Cited by 82 · see citing works
Epicardial fat and vascular risk
Katsiki, N., Mikhailidis, D. P., & Wierzbicki, A. S. (2013) · Current Opinion in Cardiology · doi:10.1097/hco.0b013e3283605fba · Cited by 77 · see citing works
Heart failure with preserved ejection fraction based on aging and comorbidities
Lin, Y. H., Fu, S., Yao, Y., Li, Y., Zhao, Y., & Luo, L. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-02935-x · Cited by 78 · see citing works
The epicardial adipose tissue and the coronary arteries: dangerous liaisons
Madonna, R., Massaro, M., Scoditti, E., Pescetelli, I., & Caterina, R. D. (2019) · Cardiovascular Research · doi:10.1093/cvr/cvz062 · Cited by 73 · see citing works
Epicardial adipose tissue: an emerging biomarker of cardiovascular complications in type 2 diabetes?
Christensen, R. H., von Scholten, B. J., Lehrskov, L. L., Rossing, P. R., & Jørgensen, P. G. (2020) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018820928824 · Cited by 72 · see citing works
Metabolic Stress and Cardiovascular Disease in Diabetes Mellitus
Chen, Y., Zhao, X., & Wu, H. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.312192 · Cited by 71 · see citing works
Chechi, K., Voisine, P., Mathieu, P., Laplante, M., Bonnet, S., Picard, F., Joubert, P., & Richard, D. (2017) · Scientific Reports · doi:10.1038/s41598-017-15501-7 · Cited by 66 · see citing works
Packer, M. (2019) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2019.09.002 · Cited by 65 · see citing works
Activin A impairs insulin action in cardiomyocytes via up-regulation of miR-143
Blumensatt, M., Greulich, S., de Wiza, D. H., Mueller, H., Maxhera, B., Rabelink, M. J. W. E., Hoeben, R. C., Akhyari, P., Al‐Hasani, H., Ruige, J. B., et al. (2013) · Cardiovascular Research · doi:10.1093/cvr/cvt173 · Cited by 64 · see citing works
Salvatore, T., Galiero, R., Caturano, A., Vetrano, E., Rinaldi, L., Coviello, F., Di Martino, A., Albanese, G., Colantuoni, S., Medicamento, G., et al. (2022) · Biomolecules · doi:10.3390/biom12020176 · Cited by 62 · see citing works
Packer, M. (2019) · European Journal of Heart Failure · doi:10.1002/ejhf.1646 · Cited by 63 · see citing works
Bone-mineral density: clinical significance, methods of quantification and forensic applications
Kranioti, E. F., Bonicelli, A., & García-Donas, J. G. (2019) · Research and Reports in Forensic Medical Science · doi:10.2147/rrfms.s164933 · Cited by 61 · see citing works
Blumensatt, M., Fahlbusch, P., Hilgers, R., Bekaert, M., de Wiza, D. H., Akhyari, P., Ruige, J. B., & Ouwens, D. M. (2016) · Basic Research in Cardiology · doi:10.1007/s00395-016-0591-0 · Cited by 59 · see citing works
Ostropolets, A., Elias, P. A., Reyes, M. V., Wan, E. Y., Pajvani, U. B., Hripcsak, G. M., & Morrow, J. (2021) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.120.009115 · Cited by 57 · see citing works
Schlich, R., Willems, M., Greulich, S., Ruppe, F., Knoefel, W. T., Ouwens, D. M., Maxhera, B., Lichtenberg, A., Eckel, J., & Sell, H. (2013) · Mediators of Inflammation · doi:10.1155/2013/982458 · Cited by 53 · see citing works
Multiple Adipose Depots Increase Cardiovascular Risk via Local and Systemic Effects
Karastergiou, K., & Fried, S. K. (2013) · Current Atherosclerosis Reports · doi:10.1007/s11883-013-0361-5 · Cited by 53 · see citing works
Impact of the cardiovascular system-associated adipose tissue on atherosclerotic pathology
Chistiakov, D. A., Grechko, A. V., Myasoedova, V. A., Melnichenko, A. А., & Orekhov, A. N. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.06.017 · Cited by 53 · see citing works
Zhao, L., Ma, Z., Guo, Z., Zheng, M., Li, K., & Yang, X. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109634 · Cited by 53 · see citing works
Packer, M. (2019) · Cardiovascular Diabetology · doi:10.1186/s12933-019-0927-9 · Cited by 52 · see citing works
Linking Arrhythmias and Adipocytes: Insights, Mechanisms, and Future Directions
Pabón, M. A., Manocha, K. K., Cheung, J. W., & Lo, J. C. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01752 · Cited by 48 · see citing works
Ariyaratnam, J., Elliott, A. D., Mishima, R. S., Gallagher, C., Lau, D. H., & Sanders, P. (2021) · Heart Rhythm O2 · doi:10.1016/j.hroo.2021.09.015 · Cited by 50 · see citing works
Inflammation and adiposity: new frontiers in atrial fibrillation
Vyas, V. S., Hunter, R. J., Longhi, M. P., & Finlay, M. (2020) · EP Europace · doi:10.1093/europace/euaa214 · Cited by 50 · see citing works
Cardio-Lipotoxicity of Epicardial Adipose Tissue
BODENSTAB, M., Varghese, R. T., & Iacobellis, G. (2024) · Biomolecules · doi:10.3390/biom14111465 · Cited by 46 · see citing works
The role of epicardial adipose tissue remodelling in heart failure with preserved ejection fraction
Janssen-Telders, C., Eringa, E. C., de Groot, J. R., de Man, F. S., & Handoko, M. L. (2025) · Cardiovascular Research · doi:10.1093/cvr/cvaf056 · Cited by 50 · see citing works
Role of novel biomarkers in diabetic cardiomyopathy
Kumrić, M., Kurir, T. T., Borovac, J. A., & Božić, J. (2021) · World Journal of Diabetes · doi:10.4239/wjd.v12.i6.685 · Cited by 47 · see citing works
Song, Y., Tan, Y., Deng, M., Shan, W., Zheng, W., Zhang, B., Cui, J., Feng, L., Shi, L., Zhang, M., et al. (2023) · MedComm · doi:10.1002/mco2.413 · Cited by 43 · see citing works
Epicardial adipose tissue: at the heart of the obesity complications
Guglielmi, V., & Sbraccia, P. (2017) · Acta Diabetologica · doi:10.1007/s00592-017-1020-z · Cited by 43 · see citing works
Chen, W. J. Y., Greulich, S., van der Meer, R. W., Rijzewijk, L. J., Lamb, H. J., Roos, A., Smit, J. W. A., Romijn, J. A., Ruige, J. B., Lammertsma, A. A., et al. (2013) · Cardiovascular Diabetology · doi:10.1186/1475-2840-12-150 · Cited by 42 · see citing works
Nesti, L., Pugliese, N. R., Chiriacò, M., Tricò, D., Baldi, S., & Natali, A. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14861 · Cited by 42 · see citing works
Zhang, J., Schmidt, C. J., & Lamont, S. J. (2017) · BMC Genomics · doi:10.1186/s12864-017-3675-9 · Cited by 39 · see citing works
Takahashi, K., Okumura, Y., Watanabe, I., Nagashima, K., Sonoda, K., Sasaki, N., Kogawa, R., Iso, K., Kurokawa, S., Ohkubo, K., et al. (2016) · Journal of Interventional Cardiac Electrophysiology · doi:10.1007/s10840-016-0130-9 · Cited by 38 · see citing works
Can We Decrease Epicardial and Pericardial Fat in Patients With Diabetes?
Muzurović, E. M., Vujošević, S., & Mikhailidis, D. P. (2021) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/10742484211006997 · Cited by 41 · see citing works
Dronkers, J., van Veldhuisen, D. J., van der Meer, P., & Meems, L. M. G. (2024) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2024.07.016 · Cited by 40 · see citing works
Serrano-Ferrer, J., Crendal, E., Walther, G., Vinet, A., Dutheil, F., Naughton, G. A., Lesourd, B., Chapier, R., Courteix, D., & Obert, P. (2016) · Metabolism · doi:10.1016/j.metabol.2016.05.006 · Cited by 36 · see citing works
Westaby, J. D., Zullo, E., Bicalho, L., Anderson, R. H., & Sheppard, M. N. (2022) · Cardiovascular Pathology · doi:10.1016/j.carpath.2022.107508 · Cited by 34 · see citing works
Karakasis, P., Pamporis, K., Theofilis, P., Milaras, N., Vlachakis, P. K., Grigoriou, K., Patoulias, D., Karamitsos, T. D., Antoniadis, A. P., & Fragakis, N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26135954 · Cited by 35 · see citing works
Philouze, C., Obert, P., Nottin, S., Benamor, A., Barthez, O., & Aboukhoudir, F. (2018) · Journal of the American Society of Echocardiography · doi:10.1016/j.echo.2017.12.006 · Cited by 34 · see citing works
Tsao, H.-M., Hu, W.-C., Tsai, P.-H., Lee, C.-L., Liu, F.-C., Wang, H.-H., Lo, L., Chang, S., Chao, T., & Chen, S. (2016) · Medicine · doi:10.1097/md.0000000000003260 · Cited by 34 · see citing works
Rohrbach, S., Troidl, C., Hamm, C. W., & Schulz, R. (2015) · IUBMB Life · doi:10.1002/iub.1352 · Cited by 33 · see citing works
Fandiño‐Vaquero, R., Fernández‐Trasancos, Á., Álvarez, E., Ahmad, S., Oliveira, A. L., Adrio, B., Fernández, Á. L., González‐Juanatey, J. R., & Eiras-Penas, S. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.05.921 · Cited by 33 · see citing works
Thermogenic potential and physiological relevance of human epicardial adipose tissue
Chechi, K., & Richard, D. (2015) · International Journal of Obesity Supplements · doi:10.1038/ijosup.2015.8 · Cited by 33 · see citing works
Potentiation of Insulin Signaling Contributes to Heart Failure in Type 2 Diabetes
Packer, M. (2018) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2018.04.003 · Cited by 32 · see citing works
Rado, S. D., Lorbeer, R., Gatidis, S., Machann, J., Storz, C., Nikolaou, K., Rathmann, W., Hoffmann, U., Peters, A., Bamberg, F., et al. (2019) · British Journal of Radiology · doi:10.1259/bjr.20180562 · Cited by 32 · see citing works
Kim, J. S., Kim, S. W., Lee, J. S., Lee, S. K., Abbott, R. D., Lee, K. Y., Lim, H. E., Sung, K., Cho, G., Koh, K. K., et al. (2021) · Cardiovascular Diabetology · doi:10.1186/s12933-021-01219-4 · Cited by 32 · see citing works
Epicardial fat density obtained with computed tomography imaging - more important than volume?
Nogajski, Ł., Mazuruk, M., Kacperska, M., Kurpias, M., Mączewski, M., Nowakowski, M., Ma̧czewski, M., Michałowska, I. M., Leszek, P., & Paterek, A. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02474-x · Cited by 31 · see citing works
Guglielmi, V., Maresca, L., D’Adamo, M., Roma, M. D., Lanzillo, C., Federici, M., Lauro, D., Preziosi, P., Bellia, A., & Sbraccia, P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103381 · Cited by 31 · see citing works
Blumensatt, M., Wronkowitz, N., Wiza, C., Cramer, A., Mueller, H., Rabelink, M. J. W. E., Hoeben, R. C., Eckel, J., Sell, H., & Ouwens, D. M. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.12.001 · Cited by 31 · see citing works
COVID-19 and Obesity: Role of Ectopic Visceral and Epicardial Adipose Tissues in Myocardial Injury
Lasbleiz, A., Gaborit, B., Soghomonian, A., Bartoli, A., Ancel, P., Jacquier, A., & Dutour, A. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.726967 · Cited by 29 · see citing works
Fernández‐Trasancos, Á., Fandiño‐Vaquero, R., Agra, R. M., Fernández, Á. L., Viñuela, J. E., González‐Juanatey, J. R., & Eiras-Penas, S. (2014) · Journal of Cellular Physiology · doi:10.1002/jcp.24619 · Cited by 29 · see citing works
Zeller, J., Krüger, C., Lamounier‐Zepter, V., Sag, S. J. M., Strack, C., Mohr, M., Loew, T. H., Schmitz, G., Maier, L. S., Fischer, M., et al. (2019) · ESC Heart Failure · doi:10.1002/ehf2.12409 · Cited by 27 · see citing works
RETRACTED: Epicardial adipose tissue and cardiac lipotoxicity: A review
Mukherjee, A. G., Renu, K., Gopalakrishnan, A. V., Jayaraj, R., Dey, A., Vellingiri, B., & Ganesan, R. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121913 · Cited by 27 · see citing works
RetractedRole of Epicardial Adipose Tissue in Health and Disease: A Matter of Fat?
Gaborit, B., Sengenès, C., Ancel, P., Jacquier, A., & Dutour, A. (2017) · Comprehensive physiology · doi:10.1002/j.2040-4603.2017.tb00767.x · Cited by 26 · see citing works
Lage, R., Moscoso, I., Fernández‐Trasancos, Á., Cebro-Márquez, M., Couselo‐Seijas, M., Fandiño‐Vaquero, R., Bravo, S. B., Sierra, J. C., González‐Juanatey, J. R., & Eiras-Penas, S. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.08.025 · Cited by 26 · see citing works
Fernández‐Trasancos, Á., Agra, R. M., García‐Acuña, J. M., Fernández, Á. L., González‐Juanatey, J. R., & Eiras-Penas, S. (2017) · Obesity · doi:10.1002/oby.21832 · Cited by 25 · see citing works
Krauz, K., Kempiński, M., Jańczak, P., Momot, K., Zarębiński, M., Poprawa, I., & Wojciechowska, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073583 · Cited by 24 · see citing works
Ballasy, N., Jadli, A. S., Edalat, P., Kang, S., Hassanabad, A. F., Gomes, K. P., Fedak, P. W. M., & Patel, V. B. (2021) · The FASEB Journal · doi:10.1096/fj.202100684rr · Cited by 24 · see citing works
Pathophysiology and clinical relevance of atrial myopathy
Tubeeckx, M. R. L., Keulenaer, G. W. D., Heidbüchel, H., & Segers, V. F. M. (2024) · Basic Research in Cardiology · doi:10.1007/s00395-024-01038-0 · Cited by 25 · see citing works
Impact of diabetes mellitus on myocardial lipid deposition: An autopsy study
Nakanishi, T., & Kato, S. (2014) · Pathology - Research and Practice · doi:10.1016/j.prp.2014.04.008 · Cited by 22 · see citing works
Kuo, C., Lu, Y., Hsu, C., Chang, C. C., Chou, R., Liu, L.-K., Chen, L., Huang, P., Chen, J., & Lin, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-27795-2 · Cited by 22 · see citing works
Menghoum, N., Badii, M. C., Leroy, M., Parra, M., Roy, C., Lejeune, S., Vancraeynest, D., Pasquet, A., Brito, D. A., Casadei, B., et al. (2025) · Cardiovascular Diabetology · doi:10.1186/s12933-025-02688-7 · Cited by 24 · see citing works
Emerging Therapy for Diabetic Cardiomyopathy: From Molecular Mechanism to Clinical Practice
Hsuan, C., Teng, S. I. F., Hsu, C., Liao, D., Chang, A. J.-W., Lee, H.-L., Hee, S., Chang, Y., & Chuang, L. (2023) · Biomedicines · doi:10.3390/biomedicines11030662 · Cited by 23 · see citing works
SGLT2 Inhibitors and How They Work Beyond the Glucosuric Effect. State of the Art
Aristizábal-Colorado, D., Ocampo-Posada, M., Martínez, W. A. R., Corredor-Rengifo, D., Rico-Fontalvo, J. E., Gómez‐Mesa, J. E., Ossman, J. J. D., & Abreu-Lomba, A. (2024) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-024-00673-1 · Cited by 21 · see citing works
Jordan, J., Toplak, H., Grassi, G. M., Yumuk, V., Kotsis, V., Engeli, S., Cuspidi, C., Nilsson, P. M., Finer, N., & Doehner, W. (2016) · Journal of Hypertension · doi:10.1097/hjh.0000000000001013 · Cited by 21 · see citing works
Ansari, M. A., Mohebati, M., Poursadegh, F., Foroughian, M., & Shamloo, A. S. (2018) · Electronic physician · doi:10.19082/7249 · Cited by 21 · see citing works
Epicardial Adipose Tissue as an Independent Cardiometabolic Risk Factor for Coronary Artery Disease
Karampetsou, N., Alexopoulos, L. G., Minia, A., Pliaka, V., Tsolakos, N., Kontzoglou, K., Perrea, D. N., & Patapis, P. (2022) · Cureus · doi:10.7759/cureus.25578 · Cited by 20 · see citing works
- Authors
- Greulich, S., Maxhera, B., Vandenplas, G., de Wiza, D. H., Smiris, K., Mueller, H., Heinrichs, J., Blumensatt, M., Cuvelier, C., Akhyari, P., Ruige, J. B., Ouwens, D. M., & Eckel, J.
- Affiliations
- Deutsches Diabetes-Zentrum e.V. (DE)
- From the Institute of Clinical Biochemistry and Pathobiochemistry (S.G., D.H.d.W., H.M., J.H., M.B., D.M.O.) and Paul Langerhans Group – Integrative Physiology (J.E.), German Diabetes Center, Duesseldorf, Germany; the Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany (B.M., K.S., P.A.); and the Heart Centre (G.V.), the Department of Pathology (C.C.), and the Department of Endocrinology (J.B.R., D.M.O.), Ghent University Hospital, Ghent...
- Corresponding author
- Ouwens, D. Margriet
- Venue
- Circulation
- Published
- 2012-11-06
- Volume
- 126
- Issue
- 19
- Pages
- 2324-2334
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2049514014
- Cited by
- 210
- References
- 45
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 16 · 2023: 15 · 2022: 22 · 2021: 19 · 2020: 13 · 2019: 18 · 2018: 13 · 2017: 18 · 2016: 14 · 2015: 6 · 2014: 10 · 2013: 15
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- epicardial adipose tissue, type 2 diabetes, cardiomyocyte dysfunction, cardiac contractile function, insulin action, activin A, angiopoietin-2, CD14, Smad2 phosphorylation, SERCA2a, calcium handling, conditioned medium, diabetic cardiomyopathy
- MeSH terms
- Adipose Tissue, Aged, Animals, Biopsy, Calcium, Cells, Cultured, Diabetes Mellitus, Type 2, Humans, Insulin, Male, Pericardium, Rats, Inbred Lew, Sarcomeres, Signal Transduction, Culture Media, Conditioned, Models, Animal, Activins, Myocytes, Cardiac, Angiopoietin-2, Rats, Sarcoplasmic Reticulum Calcium-Transporting ATPases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
