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.
Highlights
Perturbations of signaling in the heart and vessels of the body are the leading causes of cardiovascular disorders including coronary artery diseases (CAD) and valve heart diseases (VHD) [1]
Biochemical parameters associated with body fatness were intra-male reference ranges except for N-terminal pro B-type natriuretic peptide (NT-pro-BNP) (453.92 ± 596 pg/mL) and C-reactive protein (CRP) (0.98 ± 0.38 mg/100 mL) which are the clinical parameters currently most used for cardiac stress assessment and body inflammation
In view of the role of cAMP intracellular levels in the regulation of adipogenic and lipolytic processes driven by prostaglandin E2 (PGE2) metabolism, and the pivotal role of PTGE-2 in obesity-related disorders, we investigated the involvement of prostaglandin-endoperoxide synthase 2 (PTGES-2) in the expression of EPAC2, known as a cAMP effector and recently associated with ST2/IL-33 mechanosensitive system involved in the maladaptive heart response
Summary
Perturbations of signaling in the heart and vessels of the body are the leading causes of cardiovascular disorders including coronary artery diseases (CAD) and valve heart diseases (VHD) [1]. Obese patients are at increased risk of cardiovascular disease (CVD) and heart failure (HF) due to the hemodynamic stresses related to abnormal body mass and increase of volume overload [3]. The first effect of chronic volume overload on left ventricle (LV), directly related to fatness, is characterized by typically LV and left atria (LA) dilation, with a preserved ejection fraction (EF), suggesting proportional expansion of plasma volume with body mass. For this reason, the capacity of LV to dilate in response to hydrodynamic volume overload is impaired and disproportionate
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