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

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.

Transcriptomic Analyses Reveal the Effects of Walnut Kernel Cake on Adipose Deposition in Pig

“…Prostaglandin E2 is considered to be a biologically active substance that can promote adipocyte proliferation and fat synthesis. It can promote the differentiation and proliferation of adipocytes and increase the synthesis and deposition of fat by activating PGE2 receptors in adipocytes [52]. The up-regulation of these genes may play an important regulatory role in the process of walnut kernel cake promoting adipose deposition.…”

Can We Decrease Epicardial and Pericardial Fat in Patients With Diabetes?

“…There is also evidence that prostaglandin E2 (PGE2) biosynthetic enzyme (PTGES-2) (samples obtained by EAT biopsies) correlates with echocardiographic parameters of left ventricular (LV) enlargement: LV diameters, LV end diastolic volume, and LV masses (measured by TTE). 61 Moreover, PTGES-2 is directly associated with EPAC2 (exchange protein directly activated by cAMP isoform 2) gene (r = 0.70, P < 0.0001), a molecular inducer of ST2/IL-33 mediators involved in maladaptive heart remodeling. 61…”

“…61 Moreover, PTGES-2 is directly associated with EPAC2 (exchange protein directly activated by cAMP isoform 2) gene (r = 0.70, P < 0.0001), a molecular inducer of ST2/IL-33 mediators involved in maladaptive heart remodeling. 61…”

Effect ofn-3 long-chain polyunsaturated fatty acid intake on the eicosanoid profile in individuals with obesity and overweight: a systematic review and meta-analysis of clinical trials

“…These obesity-related comorbidities are closely linked to the presence of a persistent activation of pro-inflammatory signalling pathways in adipose tissue, which severely disrupts key metabolic checkpoints in this tissue (5) . The chronic pro-inflammatory eicosanoid synthesis is recognised as a key factor in the development of insulin resistance (6) , tissue inflammation (7) , renal injury (8) and increased cardiovascular maladaptations (9) . In addition to the heightened production of inflammatory mediators, obese adipose tissue shows an intrinsic inability to resolve uncontrolled inflammation and to restore tissue homeostasis and functionality (10) .…”