Differential released proteins between epicardial and subcutaneous fat from patients with cardiovascular disease: role on its progression and semaglutide modulation

Abstract Background The precise technologies for determining inflamed epicardial fat improved the prediction of cardiovascular disease (CVD) progression in relation to other anthropometric parameters. Some circulating markers of CVD might be the mirror of epicardial fat-endocrine activity and Semaglutide, a long-acting glucagon-like peptide 1 receptor agonist, might modulate it. Aims To study the differential released levels of mesothelial-, adiposity-, inflammation-, and extracellular matrix-related proteins between epicardial and subcutaneous fat, their role in CVD, its progression, and semaglutide modulation. Methods The study, approved by the Ethics Committee, enrolled 130 patients, who underwent cardiac surgery and were follow-up for MACE, or all-cause mortality. "Ex vivo" assay with epicardial and subcutaneous fat biopsies was performed for 24 hours and released molecules were stored until being used. Two designed multiplex were used for detecting protein levels with Luminex 200. Afterward, these proteins were quantified in circulation from patients with diabetes, obesity, and CVD before and after semaglutide treatment, as well as neutrophils transcriptome by sqRNA. Results From the studied proteins, the metabolic and adiposity proteins, RBP4, ADIPOQ, and FABP4, and endothelial inflammation, ICAM-1, and neutrophils activity, MPO, were the most released by epicardial fat. Higher levels of epithelial markers (CA125, MSLN), metabolism-related proteins (leptin, IGFBP7, and RBP4), extracellular matrix-related markers (THBS2, FAP, OPN, and COL4A1), endothelial inflammation (ICAM-1) and neutrophils activity (MPO) were observed in epicardial than subcutaneous fat. Released epicardial COL4A1 and ANP were the main predictors for all causes of mortality and released CA-125 and ICAM-1 levels for MACE. After semaglutide treatment, CA-125 circulating levels were modulated, as well as neutrophils transcriptome related to lysosomal transport and macroautophagic process. Conclusions The endocrine activity of epicardial fat is a predictor for MACE, and semaglutide might be suggested as a preventive therapy since this drug can modulate circulating levels of these proteins in patients with CVD.