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

Elena Vianello, Elena Dozio, Francesco Bandera, Marco Froldi, Emanuele Micaglio, John Lamont, Lorenza Tacchini, Gerd Schmitz, Massimiliano Marco Corsi Romanelli

Research output: Contribution to journalArticlepeer-review

Abstract

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 < 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.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume21
Issue number2
DOIs
Publication statusPublished - Jan 14 2020

Keywords

  • Adiposity
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Body Weights and Measures
  • Cardiovascular Diseases/diagnosis
  • Dinoprostone/metabolism
  • Echocardiography
  • Guanine Nucleotide Exchange Factors/metabolism
  • Heart Function Tests
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein/metabolism
  • Middle Aged
  • Overweight/complications
  • Pericardium/pathology
  • Prostaglandin-E Synthases/genetics
  • Receptors, Prostaglandin E, EP3 Subtype/genetics
  • Signal Transduction
  • Ventricular Remodeling

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this