Comparative evaluation of the expression of enzymes of the ceramide <i>de novo</i> synthesis pathway in cardiac adipose tissue and blood vessels of cardiovascular patients

Abstract

Aim. To compare the expression of enzymes of the ceramide de novo synthesis pathway in cardiac adipose tissue (AT) and blood vessels of patients with coronary artery disease (CAD) and acquired heart defects.Material and methods. The study included 20 patients with CAD and 18 patients with aortic stenosis/regurgitation. Biopsies of subcutaneous, epicardial, perivascular AT (SCAT, EAT, PVAT, respectively) were obtained during surgery. Quantitative PCR test was used to evaluate the gene expression of de novo ceramide synthesis enzymes (serine palmitoyltransferase C1 and C2: SPTLC1, SPTLC2; ceramide synthase 1-6: CERS1-6; dihydroceramide desaturase: DEGS1). Statistical analysis was performed using GraphPad Prism 8 (GraphPad Software).Results. Patients with CAD were characterized by a higher level of mRNA SPTLC1 in SCAT and EAT, SPTLC2, CERS1, producing C18 ceramides, CERS5 and CERS6, generating C14-C16 ceramides in EAT, CERS2 — in SCAT, producing long-chain ceramides C20-C24, CERS4, synthesizing very long-chain ceamides C18-C20. In PVAT, a high expression of CERS4 and CERS3, which synthesizes very long-chain ceramides C26 and higher, was revealed. DEGS1 expression was highest in SCAT and EAT. In patients with heart defects, there was a high expression of CERS3 in PVAT, CERS4 in EAT and PVAT, DEGS1 in EAT. The mRNA level of SPTLC1 in SCAT and EAT, SPTLC2 in EAT, CERS2 in all studied AT, CERS4 and 5 in EAT, DEGS1 in SCAT and EAT among patients with CAD was higher than in the comparison group.Conclusion. Regional fat depots of the heart differed in the level of expression of enzymes of the ceramide de novo synthesis pathway. The results obtained indicate the activation of ceramide synthesis along this pathway in predominantly epicardial adipocytes in coronary pathology, which may contribute to the accumulation of long-chain ceramides in the AT of this localization.