MUC-16, tumour and congestive heart failure marker, is expressed on epicardial mesothelial cells and is inversely associated with epicardial fat genesis

Abstract

Abstract Background CA-125 or mucin-16 (MUC-16) is a protector protein on epithelial luminal surfaces against physical stress through hydration process. However, some evidence suggests a role in fibrogenesis. MUC-16 can be detected in plasma after proteolytic cleavage with a predictive value for heart failure progression. Our main objective was to study the expression levels of this glycoprotein on epicardial mesothelial cells, its association with epicardial fat genesis, and biochemical markers. Methods and results We have used epicardial and subcutaneous fat from patients(n = 29) undergoing open heart surgery under informed consent and after approval by Ethics Committee. MUC-16 expression levels were detected on formalin-fixed paraffin-embedded epicardial fat biopsies with CA-125 antibody or real-time PCR on stored biopsies (n = 18) at -80ºC. Epicardial cells scraped with a scalpel were cultured and their MUC-16 expression was confirmed with a specific antibody and secondary fluorescent antibody. Primary cultures from epicardial stromal cells of 8 patients were obtained with collagenase digestion. After 15 days, adipogenesis was induced for 15 days with an adipogenic cocktail. Adipogenesis (AdipoQ) and mesothelial (ITLN-1) markers were quantified by real-time PCR on cells with and without adipogenesis. CA-125 expression levels were analyzed by real time-PCR on epicardial fat from 18 patients, as well as inflammation, fibrosis, stretch and adiposity markers levels on plasma by multiplex assay. Our results showed that MUC-16 is localized on epicardial mesothelial cells but not on adipocytes. The MUC-16-stained cells can be cultured and isolated after scraping the epicardium. The isolated epicardial stromal cells with collagenase showed a positive relationship between mesothelial maker (ITLN-1) and CA125 (Figure below). The higher presence of MUC-16 levels was inversely associated with AdipoQ after adipogenesis induction. From 8 plasma studied proteins, thrombospondin-2 (TP-2), was the best associated protein with MUC-16 on epicardial fat (r = 0,472; p = 0,48). Conclusion Epicardial cells express MUC-16. These types of cells can be isolated and cultured for studying their cleavage regulation and modulation. Epicardial stromal cells with a higher percentage of MUC-16 reduce the epicardial fat genesis. Further studies are needed for finding the main circulating plasma levels associated with epicardial MUC-16.