Novel atherogenic pathways from the differential transcriptome analysis of diabetic epicardial adipose, tissue
Open accessAbstract
Background and aim To evaluate the epicardial adipose tissue (EAT) transcriptome in comparison to subcutaneous fat (SAT) in coronary artery disease (CAD) and type 2 diabetes (T2DM).Methods and results SAT and EAT samples were obtained from subjects with T2DM and CAD (n = 5) and those without CAD with or without T2DM (=3) undergoing elective cardiac surgery. RNA-sequencing analysis was performed in both EAT and SAT. Gene enrichment analysis was conducted to identify pathways affected by the differentially expressed genes. Changes of top genes were verified by quantitative RT-PCR (qRT-PCR), western blot, and immunofluorescence. A total of 592 genes were differentially expressed in diabetic EAT, whereas there was no obvious changes in SAT transcriptome between diabetics and non-diabetics. Diabetic EAT was mainly enriched in inflammatory genes, such as Colony Stimulating Factor 3 (CSF3), Interleukin-1b (IL-1b), IL-6. KEGG pathway analysis confirmed that upregulated genes were involved in inflammatory pathways, such as Tumor Necrosis Factor (TNF), Nuclear Factor-κB (NF-κB) and advanced glycation end-products-receptor advanced glycation end products (AGE-RAGE). The overexpression of inflammatory genes in diabetic EAT was largely correlated with upregulated transcription factors such as NF-κB and FOS.Conclusions Diabetic EAT transcriptome is significantly different when compared to diabetic SAT and highly enriched with genes involved in innate immune response and endothelium, like Pentraxin3 (PTX3) and Endothelial lipase G (LIPG). EAT inflammatory genes expression could be induced by upregulated transcription factors, mainly NF-kB and FOSL, primarily activated by the overexpressed AGE-RAGE signaling. This suggests a unique and novel atherogenic pathway in diabetes.
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The EAT transcriptome of T2DM subjects is highly enriched in immune genes like Pentraxin 3 and endothelial lipase G compared to SAT from the same individuals.
“Recent genetic investigations evidence that the EAT transcriptome of T2DM subjects is highly enriched in immune genes like Pentraxin 3 and endothelial lipase G compared to SAT from the same individuals [44].”
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 [44]
EAT has a unique transcriptome enriched in genes involved in coagulation, endothelial function, phospholipase activity, apoptosis, and immune signaling, and a secretome that may be influenced by environmental, epigenetic, and genetic factors.
“EAT has a unique transcriptome enriched in genes involved in coagulation, endothelial function, phospholipase activity, apoptosis, and immune signaling, and a secretome that may be influenced by environmental, epigenetic, and genetic factors [43,44,45].”
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 [44]
Diabetic EAT has a peculiar proatherogenic transcriptome.
“Remarkably, diabetic EAT has a peculiar proatherogenic transcriptome, as recently reported [22].”
From Effects of Semaglutide Versus Dulaglutide on Epicardial Fat Thickness in Subjects with Type 2 Diabetes and Obesity (2020) · cites this paper as [22]
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Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · cited 1× · see citing works
“6 expression calculators in edgeR, DESeq2, and CuffDi ff [17-20].”
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · cited 1× · see citing works
“org) and quantified using the STAR aligner [16].”
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364 · see citing works
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464 · see citing works
Trapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 11,930 · cited 2× · see citing works
“The distribution of expression levels of all the genes was plotted to determine a cutoff for removal of lowly expressed genes [20].”
BackgroundMethodMootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · cited 2× · see citing works
“Gene Enrichment Analysis Gene enrichment analysis was performed using Enrich R [21, 22] using the differential genes found in RNAseq.”
MethodUniProt: the Universal Protein knowledgebase
Apweiler, R. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh131 · Cited by 7,535 · cited 1× · see citing works
“The tran scription factor databases were obtained from JASPAR, TFCAT and Unip rot databases [23-25].”
MethodKEGG as a reference resource for gene and protein annotation
Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M., & Tanabe, M. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1070 · Cited by 7,387 · cited 1× · see citing works
“The AGERAGE databases were obtained from the Kegg signalin g pathway, Wikipathways (WP2324) and NetPath transduction pathway [26-27].”
MethodHuman 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 · cited 3× · see citing works
“EAT has unique embryolog ic and anatomic features, including smaller adipocytes , brown-fat like thermogenic and cardio-protective properties, greater fatty acid breakdown and higher inflammatory infiltrate when compared to subcutaneous adipose tissue (SAT) [1-8].”
BackgroundResultRAGE Mediates a Novel Proinflammatory Axis
Hofmann, M. A., Drury, S., Fu, C., Qu, W., Taguchi, A., Lu, Y., Avila, C., Kambham, N., Bierhaus, A., Nawroth, P., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80801-6 · Cited by 1,864 · see citing works
JASPAR: an open-access database for eukaryotic transcription factor binding profiles
Sandelin, A. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh012 · Cited by 1,763 · cited 1× · see citing works
“The tran scription factor databases were obtained from JASPAR, TFCAT and Unip rot databases [23-25].”
MethodHTSeq – A Python framework to work with high-throughput sequencing dataPreprint
Anders, S., Pyl, P. T., & Huber, W. K. (2014) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/002824 · Cited by 1,286 · see citing works
Delerive, P., De Bosscher, K., Besnard, S., Vanden Berghe, W., Peters, J. M., Gonzalez, F. J., Fruchart, J.-C., Tedgui, A., Haegeman, G., & Staels, B. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.32048 · Cited by 1,089 · 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 · cited 2× · see citing works
“EAT has unique embryolog ic and anatomic features, including smaller adipocytes , brown-fat like thermogenic and cardio-protective properties, greater fatty acid breakdown and higher inflammatory infiltrate when compared to subcutaneous adipose tissue (SAT) [1-8].”
BackgroundHuman 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
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 · cited 2× · see citing works
“EAT has unique embryolog ic and anatomic features, including smaller adipocytes , brown-fat like thermogenic and cardio-protective properties, greater fatty acid breakdown and higher inflammatory infiltrate when compared to subcutaneous adipose tissue (SAT) [1-8].”
BackgroundEpicardial adipose tissue: emerging physiological, pathophysiological and clinical features
Iacobellis, G., & Bianco, A. C. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2011.07.003 · Cited by 601 · see citing works
Verde, E. R., Lee‐Osbourne, J., Worley, P. F., Malinow, R., & Cline, H. T. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.031 · Cited by 403 · cited 1× · see citing works
“ARC plays a role in homeostatic regulation of synaptic strength and its expression is increased by strong sy aptic activation [41].”
BackgroundEpicardial adipose tissue and insulin resistance in obese subjects
Iacobellis, G., & Leonetti, F. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1087 · Cited by 355 · cited 1× · see citing works
“EAT was independently correlated with insulin resis tance [43-44].”
BackgroundVisceral adipose tissue as a source of inflammation and promoter of atherosclerosis
Alexopoulos, N. A., Katritsis, D. G., & Raggi, P. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.12.023 · Cited by 333 · see citing works
Sacks, H. S., Fain, J. N., Holman, B., Cheema, P. S., Chary, A., Parks, F., Karas, J. G., Optican, R. J., Bahouth, S. W., Garrett, E., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0571 · Cited by 320 · cited 1× · see citing works
“EAT has unique embryolog ic and anatomic features, including smaller adipocytes , brown-fat like thermogenic and cardio-protective properties, greater fatty acid breakdown and higher inflammatory infiltrate when compared to subcutaneous adipose tissue (SAT) [1-8].”
BackgroundMyocardial, Perivascular, and Epicardial Fat
Iozzo, P. (2011) · Diabetes Care · doi:10.2337/dc11-s250 · Cited by 272 · cited 1× · see citing works
“Emerging and considerable evidence indicates an act ive interplay between dysfunctional fat cells, visc eral adiposity and diabetes-related coronary atheroscler osis [12-14].”
BackgroundThe G0/G1 switch gene 2 is a novel PPAR target gene
Zandbergen, F. J., Mandard, S., Escher, P., Tan, N. S., Patsouris, D., Jatkoe, T., Rojas-Caro, S., Madore, S., Wahli, W., Tafuri, S. R., et al. (2005) · Biochemical Journal · doi:10.1042/bj20050636 · Cited by 228 · see citing works
TFCat: the curated catalog of mouse and human transcription factors
Fulton, D. L., Sundararajan, S., Badis, G., Hughes, T. R., Wasserman, W. W., Roach, J. C., & SLADEK, R. M. (2009) · Genome biology · doi:10.1186/gb-2009-10-3-r29 · Cited by 207 · cited 1× · see citing works
“The tran scription factor databases were obtained from JASPAR, TFCAT and Unip rot databases [23-25].”
MethodCOOPER, M. (2004) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2004.08.021 · Cited by 172 · cited 1× · see citing works
“Notably, 20 upregulated genes in diabet c EAT belonged to the AGE-RAGE signaling which is known to play a key role in the diabetes-accelerate d atherosclerosis throughout the activation of proinflammatory and pro-fibrotic pathways [29].”
BackgroundKarastergiou, 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
Norata, G. D., Garlanda, C., & Catapano, A. L. (2010) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2010.03.005 · Cited by 155 · see citing works
Baker, A. R., Harte, A. L., Howell, N., Pritlove, D. C., Ranasinghe, A. M., da Silva, N. F., Youssef, E. M., Khunti, K. K., Davies, M. J., Bonser, R. S., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2579 · Cited by 131 · see citing works
Epicardial adipose tissue has a unique transcriptome modified in severe coronary artery disease
McAninch, E. A., Fonseca, T. L., Poggioli, R., Panos, A. L., Salerno, T. A., Deng, Y., Li, Y., Bianco, A. C., & Iacobellis, G. (2015) · Obesity · doi:10.1002/oby.21059 · Cited by 130 · see citing works
Sacks, H. S., Fain, J. N., Cheema, P., Bahouth, S. W., Garrett, E., Wolf, R. Y., Wolford, D., & Samaha, J. (2011) · Diabetes Care · doi:10.2337/dc10-2083 · Cited by 121 · see citing works
Bambace, C., Telesca, M., Zoico, E., Sepe, A., Olioso, D., Rossi, A. P., Corzato, F., Francesco, V. D., Mazzucco, A., Santini, F., et al. (2010) · Cardiovascular Pathology · doi:10.1016/j.carpath.2010.07.005 · Cited by 114 · see citing works
Dutour, A., Achard, V., Sell, H., Naour, N., Collart, F., Gaborit, B., Silaghi, C. A., Eckel, J., Alessi, M., Hénégar, C., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1222 · Cited by 101 · see citing works
Regulatory long non-coding RNA and its functions
Huang, Y., Liu, N., Wang, J., Wang, Y. Q., Yu, X. L., Wang, Z. B., Cheng, X. C., & Zou, Q. (2012) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-012-0166-y · Cited by 96 · cited 1× · see citing works
“Al though their function is unclear, lncRNAs can regulate gene expression at epigenetic, transcription, and post-transcription levels and participate in various physiological and pathological processes [40].”
BackgroundHighly efficient method for isolation of total RNA from adipose tissue
Cirera, S. (2013) · BMC Research Notes · doi:10.1186/1756-0500-6-472 · Cited by 62 · see citing works
Fracanzani, A. L., Pisano, G., Consonni, D., Tiraboschi, S., Baragetti, A., Bertelli, C., Norata, G. D., Dongiovanni, P., Valenti, L. V. C., Grigore, L., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162473 · Cited by 53 · see citing works
Distel, E., Penot, G., Cadoudal, T., Balguy, I., Durant, S., & Benelli, C. (2012) · Biochimie · doi:10.1016/j.biochi.2012.04.014 · Cited by 49 · cited 1× · see citing works
“Treatment w ith pioglitazone was associated with a reduction of proinflammatory and anti-inflammatory genes in EAT in T2DM patients with CAD [39].”
BackgroundPericoronary Adipose Tissue: A Novel Therapeutic Target in Obesity-Related Coronary Atherosclerosis
Mazurek, T., & Opolski, G. (2015) · Journal of the American College of Nutrition · doi:10.1080/07315724.2014.933685 · Cited by 48 · cited 1× · see citing works
“Emerging and considerable evidence indicates an act ive interplay between dysfunctional fat cells, visc eral adiposity and diabetes-related coronary atheroscler osis [12-14].”
BackgroundGuauque-Olarte, S., Gaudreault, N., Piché, M., Fournier, D., Mauriège, P., Mathieu, P., & Bossé, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019908 · Cited by 47 · cited 2× · see citing works
“Microarray analysis from ours and other groups found EAT to be highly enriched with g enes involved in inflammation, coagulation, immune signaling, potassium transport and apoptosis when c ompared to SAT in subjects with CAD [9-11].”
MethodResultDozio, E., Vianello, E., Briganti, S., Lamont, J. V., Tacchini, L., Schmitz, G., & Romanelli, M. M. C. (2015) · Journal of Diabetes Research · doi:10.1155/2016/2327341 · Cited by 39 · see citing works
Vergeer, M., Cohn, D. M., Boekholdt, S. M., Sandhu, M. S., Prins, H. M., Ricketts, S. L., Wareham, N. J., Kastelein, J. J. P., Khaw, K., Kamphuisen, P. W., et al. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.04.004 · Cited by 38 · see citing works
Adiponectin and p53 mRNA in epicardial and subcutaneous fat from heart failure patients
Agra, R. M., Teijeira‐Fernández, E., Pascual-Figal, D. A., Sánchez‐Más, J., Fernández‐Trasancos, Á., González‐Juanatey, J. R., & Eiras-Penas, S. (2013) · European Journal of Clinical Investigation · doi:10.1111/eci.12186 · Cited by 37 · cited 1× · see citing works
“Particularly, CDKN1A and GDF15 are members of the p53 signaling pathway, which ha s previously been shown to be implicated in both oxidative stress and car iovascular disease [42].”
BackgroundAminotransferase activity in morbid and uncomplicated obesity: Predictive role of fasting insulin
Iacobellis, G., Moschetta, A., Buzzetti, R., Ribaudo, M. C., Baroni, M. G., & Leonetti, F. (2006) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2006.02.008 · Cited by 24 · see citing works
Association of endothelial lipase gene−384A/C with coronary artery disease in Han Chinese people
Xie, L., Sun, Y., Yu, T., Liu, Y., & Deng, Y. (2015) · BMJ Open · doi:10.1136/bmjopen-2015-007621 · Cited by 15 · cited 1× · see citing works
“LIPG is a gene involved in the lipid uptake, endothelium regulation and may be involved in the pathogenesis of CAD, although results are controversial [34-35].”
ResultEchocardiographic epicardial fat: A new tool in the white coat pocket
Iacobellis, G. (2008) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2008.06.007 · Cited by 11 · see citing works
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Epicardial adipose tissue in contemporary cardiology
Iacobellis, G. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00679-9 · Cited by 797 · see citing works
Self-citationSGLT2 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
Egaña-Gorroño, L., López‐Díez, R., Yepuri, G., Ramirez, L. S., Reverdatto, S., Gugger, P. F., Shekhtman, A. G., Ramasamy, R., & Schmidt, A. M. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00037 · Cited by 210 · see citing works
“The diabetic EAT-associated genes were largely linked to inflammation (IL1B and IL6); KEGG pathway analysis placed these differentially-expressed genes in the TNF, NF-κB, andAGERAGE pathways (110).”
BackgroundInfluentialNon-canonical WNT signalling in cardiovascular disease: mechanisms and therapeutic implications
Akoumianakis, I., Polkinghorne, M., & Antoniades, C. A. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00718-5 · Cited by 162 · see citing works
Iacobellis, G., & Villasante Fricke, A. C. (2020) · Journal of the Endocrine Society · doi:10.1210/jendso/bvz042 · Cited by 168 · see citing works
“Remarkably, diabetic EAT has a peculiar proatherogenic transcriptome, as recently reported [22].”
BackgroundDozio, E., Vianello, E., Malavazos, A. E., Tacchini, L., Schmitz, G., Iacobellis, G., & Corsi Romanelli, M. M. (2019) · International Journal of Cardiology · doi:10.1016/j.ijcard.2019.04.039 · Cited by 118 · see citing works
Self-citationApplications of SGLT2 inhibitors beyond glycaemic control
O’Hara, D. V., Lam, C. S. P., McMurray, J. J. V., Yi, T. W., HOCKING, S. L., Dawson, J., Raichand, S., Januszewski, A. S., & Jardine, M. (2024) · Nature Reviews Nephrology · doi:10.1038/s41581-024-00836-y · Cited by 111 · see citing works
“In people with T2DM, epicardial fat produces profibrotic and pro-inflammatory mediators with potential adverse effects on the myocardium 52 .”
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: 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
Epicardial adipose tissue as a mediator of cardiac arrhythmias
Patel, K. H. K., Hwang, T., Liebers, C. S., & Ng, F. S. (2021) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00565.2021 · Cited by 73 · see citing works
Adipose tissue depot differences in adipokines and effects on skeletal and cardiac muscle
Rodrı́guez, A., Becerril, S., Hernández‐Pardos, A. W., & Frühbeck, G. (2020) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2020.04.003 · Cited by 63 · 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
“Recent genetic investigations evidence that the EAT transcriptome of T2DM subjects is highly enriched in immune genes like Pentraxin 3 and endothelial lipase G compared to SAT from the same individuals [44].”
BackgroundIacobellis, G., & Baroni, M. G. (2021) · Journal of Endocrinological Investigation · doi:10.1007/s40618-021-01687-1 · Cited by 58 · see citing works
Browning Epicardial Adipose Tissue: Friend or Foe?
Doukbi, E., Soghomonian, A., Sengenès, C., Ahmed, S., Ancel, P., Dutour, A., & Gaborit, B. (2022) · Cells · doi:10.3390/cells11060991 · Cited by 56 · see citing works
Epicardial fat links obesity to cardiovascular diseases
Iacobellis, G. (2023) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2023.04.006 · Cited by 54 · see citing works
Elsanhoury, A., Nelki, V., Kelle, S., Van Linthout, S., & Tschöpe, C. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.720690 · Cited by 51 · see citing works
“In diabetics, the EAT transcriptome is rich in proinflammatory and innate immune genes like Pentraxin 3 (PTX3) and endothelial lipase G (LIPG) compared with the subcutaneous fat transcriptome from the same patients (64).”
BackgroundMiller, R. J. H., Shanbhag, A. D., Killekar, A., Lemley, M. H., Bednarski, B. P., Kriekinge, S. D. V., Kavanagh, P., Fehér, A., Miller, E. J., Einstein, A. J., et al. (2024) · npj Digital Medicine · doi:10.1038/s41746-024-01020-z · Cited by 46 · 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
“These proteins include lipase G (LIPG), solute carrier family 7 member 5 (SLC7A5), and solute carrier family 16 member 10 (SLC16A10) [44].”
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
“Metformin monotherapy significantly decreases EAT thickness and BMI, in patients with IR120 and T2DM.121 In children with obesity (n ¼ 30 patients with IR; mean age 14.3 + 2.1 years; BMI 34.0 + 7.6 kg/m2; EAT measured by TTE), treatment with metformin (after 3 months) reduced EAT thickness (6.4 + 2.1 vs 4.7 + 2.0 mm;…”
ResultInfluentialEffect of glucagon-like peptide-1 (GLP-1) analogues on epicardial adipose tissue: A meta-analysis
Berg, G., Barchuk, M., Lobo, M., & Nogueira, J. P. (2022) · Diabetes & Metabolic Syndrome: Clinical Research & Reviews · doi:10.1016/j.dsx.2022.102562 · Cited by 36 · see citing works
Molecular Mechanisms of Type 2 Diabetes-Related Heart Disease and Therapeutic Insights
Giraldo, G. C., Román-Gonzaléz, A., Cañas, F., & García, A. M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104548 · Cited by 37 · see citing works
“…and cardiomyocyte apoptosis induce activation of TLR2 and TLR4 along with increased NLRP3, driving the pro-caspase-1 recruitment for inflammasome formation, amplifying myocardial cytokine production, macrophage infiltration, and cardiomyocyte apoptosis and peripheral cardiac fibrosis [26,29–31].”
Mráz, M., Cinkajzlová, A., Kloučková, J., Lacinová, Z., Kratochvílová, H., Lipš, M., Pořízka, M., Kopecký, P., Lindner, J., Kotulák, T., et al. (2019) · Mediators of Inflammation · doi:10.1155/2019/5481725 · Cited by 34 · see citing works
“This hypothesis is supported by a recent transcriptomic analysis showing increased expression of a number of proinflammatory genes involved in TNF-α, NF-κB, and other inflammatory pathways in EAT from diabetic relative to nondiabetic individuals [29].”
Is epicardial fat attenuation a novel marker of coronary inflammation?
Iacobellis, G., & Mahabadi, A. A. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.02.023 · Cited by 34 · see citing works
Association of Circulating, Inflammatory-Response Exosomal mRNAs With Acute Myocardial Infarction
He, G., Huang, Y., Liu, L., Huang, J., Lo, K. K.-H., Yu, Y., Chen, C., Zhang, B., & Feng, Y. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.712061 · Cited by 26 · see citing works
Pierzynová, A., Šrámek, J., Cinkajzlová, A., Kratochvílová, H., Lindner, J., Haluzı́k, M., & Kučera, T. (2019) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2019.05.063 · 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
Li, Y., Ping, X., Zhang, Y., Li, G., Zhang, T., Chen, G., Ma, X., Wang, D., & Xu, L. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.667698 · Cited by 20 · 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
“Lipotoxicity is deemed to be another pathophysiology mechanism which promotes EAT-induced coronary atherosclerosis [60].”
BackgroundInfluentialLiraglutide effects on epicardial adipose tissue micro-RNAs and intra-operative glucose control
Iacobellis, G., Goldberger, J. J., Lamelas, J., Martinez, C. A., Sterling, C. M., BODENSTAB, M., & Frasca, D. (2024) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2024.08.019 · Cited by 19 · see citing works
Barchuk, M., Schreier, L. E., Lopez, G. I., Cevey, Á. C., Baldi, J., Tome, M. C. F., Goren, N., Rubio, M., Miksztowicz, V., & Berg, G. A. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.06.915 · Cited by 19 · see citing works
The RAGE/DIAPH1 axis: mediator of obesity and proposed biomarker of human cardiometabolic disease
Arivazhagan, L., Popp, C. J., Ruiz, H. H., Wilson, R. A., Manigrasso, M. B., Shekhtman, A. G., Ramasamy, R., Sevick, M. A., & Schmidt, A. M. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac175 · Cited by 15 · see citing works
Wróblewski, A. M., Strycharz, J., Oszajca, K., Czarny, P. L., Świderska, E., Matyjas, T., Zieleniak, A., Rucińska, M., Pomorski, L., Drzewoski, J., et al. (2023) · Medical Science Monitor · doi:10.12659/msm.939299 · Cited by 15 · see citing works
Doukbi, E., Ancel, P., Dutour, A., Soghomonian, A., Ahmed, S., Castejon, V., Pipéroglou, C., Gariboldi, V., Lenoir, M., Lechevallier, É., et al. (2024) · Obesity · doi:10.1002/oby.24023 · Cited by 15 · see citing works
“In the past few years, its secretome was shown to switch into a proinflammatory profile in obesity and coronary artery disease (CAD) inducing atherogenic changes in monocytes [6, 7].”
BackgroundZhao, Y. X., Zhu, H., Pan, H., Liu, X. M., Wang, L. J., Yang, H. B., Li, N., Gong, F., Sun, W., & Zeng, Y. (2019) · International Journal of Endocrinology · doi:10.1155/2019/6976712 · Cited by 14 · see citing works
“During atherosclerosis, this pathway plays a protective role inhibiting NF-𝜅B pathway to alleviate oxygen stress and restrain proliferation of smooth muscle cells to postpone development of atherosclerosis [22– 25].”
InfluentialDiverging Role of Epicardial Adipose Tissue Across the Entire Heart Failure Spectrum
Rossi, V. A., Nebunu, D., Haider, T., Laptseva, N., Naegele, M. P., Ruschitzka, F. T., Sudano, I., & Flammer, A. J. (2023) · ESC Heart Failure · doi:10.1002/ehf2.14483 · Cited by 12 · see citing works
“31 All together, these factors may promote systemic atherosclerosis, resulting in increased arterial stiffness and reduced endothelial NO production.”
BackgroundVincenzi, M., & Nebigil, C. G. (2025) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2025.02.006 · Cited by 10 · see citing works
Youk, H., Kim, M., Lee, C. J., Oh, J., Park, S., Kang, S., Kim, J., Ann, S.-J., & Lee, S. (2020) · Korean Circulation Journal · doi:10.4070/kcj.2020.0117 · Cited by 10 · see citing works
Marcon, L. M. R., & Mazzieri, A. (2025) · Immuno · doi:10.3390/immuno5010011 · Cited by 9 · see citing works
“Studies suggest that the pathogenetic mechanisms of diabetic coronaropathy include upregulation of signaling between AGEs and their receptors in EAT [34].”
Flinn, B. B., Adams, C., Chowdhury, N. C., Gress, T., & Santanam, N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105297 · Cited by 9 · see citing works
SGLT2 inhibitors: a new pillar of the heart failure regimen
DeSa, T. B., & Gong, T. (2021) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2204133 · Cited by 9 · see citing works
Sun, Y., Li, X.-G., Xu, K., Hou, J., You, H., Zhang, R., Qi, M., Zhang, L., Xu, L., Greenwald, S. E., et al. (2022) · BMC Cardiovascular Disorders · doi:10.1186/s12872-022-02527-7 · Cited by 8 · see citing works
“This hypothesis is supported by evidence that several genes involved in cellular function are downregulated in the epicardial adipocytes of advanced CAD [15].”
BackgroundTargeting Epicardial Fat in Obesity and Diabetes Pharmacotherapy
Iacobellis, G., Basilico, S., & Malavazos, A. E. (2022) · Handbook of experimental pharmacology · doi:10.1007/164_2021_577 · Cited by 8 · see citing works
Benefits of GLP-1 Mimetics on Epicardial Adiposity
Yaribeygi, H., Maleki, M., Nasimi, F. S., Jamialahmadi, T., Stanford, F. C., & Sahebkar, A. (2023) · Current Medicinal Chemistry · doi:10.2174/0929867330666230113110431 · Cited by 6 · see citing works
Epicardial fat thickness in type 2 diabetes outpatient care
Iacobellis, G., Goldberger, J. J., Malavazos, A. E., Sterling, C. M., & Canturk, A. (2023) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2023.10.016 · Cited by 6 · see citing works
Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study
Neeland, I. J., Zhu, F., Graça, G., Lymperopoulos, A., Iacobellis, G., Farzaneh, A., Bos, D., Ghanbari, M., Goldberger, J. J., Kavousi, M., et al. (2025) · Journal of the American Heart Association · doi:10.1161/jaha.124.039750 · Cited by 5 · see citing works
“29 We also found that glycoproteins were significantly positively associated with EAT in both the *Baseline refers to the date that the blood sample used for metabolomics profiling was obtained.”
Barchuk, M., Nagasawa, T., Murakami, M., Lopez, G. I., Baldi, J., Miksztowicz, V., Rubio, M., Schreier, L. E., Nakajima, K., & Berg, G. A. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.08.001 · Cited by 5 · see citing works
Brăescu, L., Sturza, A., Șoșdean, R., Aburel, O. M., Lazar, M. A., Muntean, D. M., Luca, C. T., Brie, D. M., Feier, H. B., Crișan, S., et al. (2024) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2024-0188 · Cited by 4 · see citing works
Dittfeld, C., Bienger, K., Andres, J., Plötze, K., Jannasch, A., Waldow, T., Tugtekin, S., & Matschke, K. (2018) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-170341 · Cited by 4 · see citing works
Closs, C., Vargas‐Uricoechea, H., Schwarzstein, D., Lobo, M., Lagranja, E. S., Leiva, E. G., & Nogueira, J. P. (2023) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2023.101674 · Cited by 3 · see citing works
Coronary Artery Disease and Epicardial Adipose Tissue
Iacobellis, G. (2020) · Contemporary cardiology · doi:10.1007/978-3-030-40570-0_8 · Cited by 3 · see citing works
Cernea, S., Roiban, A. L., Onișor, D. M., & Raț, N. (2025) · Reviews in Cardiovascular Medicine · doi:10.31083/rcm39534 · Cited by 2 · see citing works
“In patients with diabetes mellitus (DM), hyperglycemia-associated upregulation of signaling through the binding of the advanced glycation end products to their receptors further contribute to these mechanisms by increasing oxidative stress and causing endothelial damage [1,3].”
Mahan, W., Gao, H., Liu, N., Zhao, Z., & Huang, Y. (2025) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-025-05688-1 · Cited by 2 · see citing works
“It has been reported that LncRNAs can regulate post-transcriptional gene levels, are involved in a variety of physiological processes, and are potential predictive or diagnostic biomarkers for many diseases [25, 26].”
Pagel, P. S., Hang, D., Freed, J. K., & Crystal, G. J. (2025) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2025.06.015 · Cited by 2 · see citing works
Kuleta, K., Krauz, K., Żmuda, J., Momot, K., Zarębiński, M., Poprawa, I., & Wojciechowska, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199271 · Cited by 2 · see citing works
Aboukhoudir, F., Philouze, C., Grandperrin, A., Nottin, S., & Obert, P. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.991415 · Cited by 2 · see citing works
“Indeed, while being cardioprotective in a physiological context, this adipose tissue switches to a deleterious, pro-inflammatory secretory profile in a pathological environment (51, 52).”
BackgroundАнатольевна, К. О., Kravchenko, E. S., Naryzhnaya, N. V., Кологривова, И. В., Сергеевна, К. А., Анатольевна, Х. О., Sviazova, N., Andreev, S. L., & Суслова, Т. Е. (2024) · Kardiologiia · doi:10.18087/cardio.2024.9.n2691 · Cited by 1 · see citing works
Cardiometabolic Risk and Epicardial Adipose Tissue
Iacobellis, G., & Fricke, A. C. V. (2020) · Contemporary cardiology · doi:10.1007/978-3-030-40570-0_13
Transcriptomic and Proteomic Analysis of the Epicardial Adipose Tissue
Camarena, V., Sant, D., Huff, T. C., & Wang, G. (2020) · Contemporary cardiology · doi:10.1007/978-3-030-40570-0_3
Drug-induced metabolic alterations in adipose tissue - with an emphasis in epicardial adipose tissue
Pinho, A. C. O., Burgeiro, A., Pereira, M. J., & Carvalho, E. (2022) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765202220201819
Az SGLT2-gátlók lehetséges hatásai a kardiovaszkuláris megbetegedésekben
Kosztin, A. (2023) · Cardiologia Hungarica · doi:10.26430/chungarica.2023.53.4.360
“Az epikardiális zsír egy metabolikusan rendkívül aktív szövet, amely különösen cukorbetegeknél profibrotikus és gyulladást elősegítő citokineket választ ki, amely hátrányosan befolyásolhatja a szívizom funkcióját és a koszorúérrendszert (29).”
Omics Insights into Epicardial Adipose Tissue: Unravelling Its Molecular Landscape
Mitu, I., Popescu, R. M., Dimitriu, C.-D., Miftode, R.-Ş., Costache, I. I., & Mitu, O. (2024) · Applied Sciences · doi:10.3390/app14104173
Tessuto adiposo epicardico: dagli aspetti biomolecolari alla pratica clinica
Malavazos, A. E., Dubini, C., Meregalli, C., Boniardi, F., Secchi, F., Piepoli, M. F., Salvetti, G., Menicanti, L., Chessa, M., Spagnolo, P., et al. (2024) · L Endocrinologo · doi:10.1007/s40619-024-01493-w
Szydełko, J., Zapolski, T., Lenart-Lipińska, M., Czop, M., Petniak, A., Kocki, J., & Matyjaszek‐Matuszek, B. (2026) · Cardiovascular Diabetology · doi:10.1186/s12933-025-03055-2
“Leveraging transcriptome and secretome analyses of EAT from T2DM and CAD patients, increased expression of pro-inflammatory adipokines and cytokines, such as IL-6, interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) was detected [66–68].”
Smith, B., Bellinge, B., Francis, R. J., Parry, R., Lee, S. C., Bellinge, J. W., & Schultz, C. J. (2026) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2026.109316
Opstad, T. B., Opdahl, F. L., Larsen, S., Åkra, S., Palmero, S., Tønnessen, T., Solheim, S., Alexander, J., Alehagen, U., & Lunde, I. G. (2026) · Antioxidants · doi:10.3390/antiox15060687
“Previous reports show that selenoproteins are highly present in EAT, underpinning their impact in this environment [14–20].”
InfluentialSagan, D., Góral, M., Siedlecki, R., Fidorowicz, D., Sergiel, K. H., Torbacka, E., Skuza, A. I., Downar-Zapolska, M., Mikłaszewicz, A., & Bednarczuk, K. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.2(50).2026.5476
Đuzel, A., Rotkvić, P. G., Babić, Z., Šipoš, I. H., Bekić, M., Bratičević, M. N., Rotkvić, L., & Berković, M. C. (2026) · Medicina · doi:10.3390/medicina62071402
“The transcriptome of EAT in T2DM patients differs significantly from that of SAT, highlighting heightened involvement of innate immune response and lipid metabolism pathways, primarily driven by the AGE-RAGE signaling mechanism [8].”
- Authors
- Camarena, V., Sant, D., Mohseni, M., Salerno, T., Zaleski, M. L., Wang, G., & Iacobellis, G.
- Affiliations
- Dr. John T. Macdonald Foundation (US)
- University of Miami (US)
- Corresponding author
- Wang, G.
- Iacobellis, G.
- Venue
- Nutrition Metabolism and Cardiovascular Diseases
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 27
- Issue
- 8
- Pages
- 739-750
- ISSN
- 0939-4753 (ISSN-L)
- PMC
- PMC7540222
- OpenAlex
- W2623528424
- Cited by
- 67
- References
- 44
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 10 · 2023: 7 · 2022: 12 · 2021: 7 · 2020: 10 · 2019: 6 · 2018: 2
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nutrition Metabolism and Cardiovascular Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1R01NS089525)
- James and Esther King Biomedical Research Award (3KN08)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- epicardial adipose tissue, subcutaneous adipose tissue, type 2 diabetes, coronary artery disease, atherogenesis, inflammation, NF-κB signaling, AGE-RAGE signaling pathway, innate immune response, pentraxin 3, transcriptome, differentially expressed genes
- MeSH terms
- Adipose Tissue, Aged, Coronary Artery Disease, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Female, Humans, Inflammation, Male, Middle Aged, Pericardium, Phenotype, Risk Factors, RNA, Messenger, Cytokines, Sequence Analysis, RNA, Genetic Predisposition to Disease, Gene Expression Profiling, Subcutaneous Fat, Atherosclerosis, Adipokines, Transcriptome
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