{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T23:56:54Z","timestamp":1767830214692,"version":"3.49.0"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T00:00:00Z","timestamp":1578960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There is recent evidence that the dysfunctional responses of a peculiar visceral fat deposit known as epicardial adipose tissue (EAT) can directly promote cardiac enlargement in the case of obesity. Here, we observed a newer molecular pattern associated with LV dysfunction mediated by prostaglandin E2 (PGE2) deregulation in EAT in a cardiovascular disease (CVD) population. A series of 33 overweight CVD males were enrolled and their EAT thickness, LV mass, and volumes were measured by echocardiography. Blood, plasma, EAT, and SAT biopsies were collected for molecular and proteomic assays. Our data show that PGE2 biosynthetic enzyme (PTGES-2) correlates with echocardiographic parameters of LV enlargement: LV diameters, LV end diastolic volume, and LV masses. Moreover, PTGES-2 is directly associated with EPAC2 gene (r = 0.70, p &lt; 0.0001), known as a molecular inducer of ST2\/IL-33 mediators involved in maladaptive heart remodelling. Furthermore, PGE2 receptor 3 (PTEGER3) results are downregulated and its expression is inversely associated with ST2\/IL-33 expression. Contrarily, PGE2 receptor 4 (PTGER4) is upregulated in EAT and directly correlates with ST2 molecular expression. Our data suggest that excessive body fatness can shift the EAT transcriptome to a pro-tissue remodelling profile, may be driven by PGE2 deregulation, with consequent promotion of EPAC2 and ST2 signalling.<\/jats:p>","DOI":"10.3390\/ijms21020520","type":"journal-article","created":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T10:30:27Z","timestamp":1579084227000},"page":"520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Correlative Study on Impaired Prostaglandin E2 Regulation in Epicardial Adipose Tissue and Its Role in Maladaptive Cardiac Remodeling via EPAC2 and ST2 Signaling in Overweight Cardiovascular Disease Subjects"],"prefix":"10.3390","volume":"21","author":[{"given":"Elena","family":"Vianello","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5833-0780","authenticated-orcid":false,"given":"Elena","family":"Dozio","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Bandera","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy"},{"name":"Cardiology University Department, Heart Failure Unit, IRCCS Policlinico San Donato, 20097 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Froldi","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"},{"name":"Internal Medicine Unit IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele","family":"Micaglio","sequence":"additional","affiliation":[{"name":"U.O.C. SMEL-1 of Clinical Pathology, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Lamont","sequence":"additional","affiliation":[{"name":"Randox Laboratories LTD, R&amp;D, Crumlin-Antrim, Belfast, BT29, Northen Ireland, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenza","family":"Tacchini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimiliano Marco","family":"Corsi Romanelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy"},{"name":"U.O.C. SMEL-1 of Clinical Pathology, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.trsl.2014.05.001","article-title":"Obesity, metabolic dysfunction, and cardiac fibrosis: Pathophysiological pathways, molecular mechanisms, and therapeutic opportunities","volume":"164","author":"Cavalera","year":"2014","journal-title":"Transl. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1161\/CIRCRESAHA.115.306885","article-title":"Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease","volume":"118","author":"Fuster","year":"2016","journal-title":"Circ. 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