Expression of Ceramide-Metabolizing Enzymes in the Heart Adipose Tissue of Cardiovascular Disease Patients

Int J Mol Sci. 2023 May 30;24(11):9494. doi: 10.3390/ijms24119494.

Abstract

Here, we examined the expression of ceramide metabolism enzymes in the subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT) of 30 patients with coronary artery disease (CAD) and 30 patients with valvular heart disease (VHD) by means of quantitative polymerase chain reaction and fluorescent Western blotting. The EAT of patients with CAD showed higher expression of the genes responsible for ceramide biosynthesis (SPTLC1, SPTLC2, CERS1, 5, 6, DEGS1, and SMPD1) and utilization (ASAH1, SGMS1). PVAT was characterized by higher mRNA levels of CERS3, CERS4, DEGS1, SMPD1, and ceramide utilization enzyme (SGMS2). In patients with VHD, there was a high CERS4, DEGS1, and SGMS2 expression in the EAT and CERS3 and CERS4 expression in the PVAT. Among patients with CAD, the expression of SPTLC1 in SAT and EAT, SPTLC2 in EAT, CERS2 in all studied AT, CERS4 and CERS5 in EAT, DEGS1 in SAT and EAT, ASAH1 in all studied AT, and SGMS1 in EAT was higher than in those with VHD. Protein levels of ceramide-metabolizing enzymes were consistent with gene expression trends. The obtained results indicate an activation of ceramide synthesis de novo and from sphingomyelin in cardiovascular disease, mainly in EAT, that contributes to the accumulation of ceramides in this location.

Keywords: ceramidase; ceramide synthase; ceramides; coronary artery disease; epicardial adipose tissue; serine palmitoyltransferase; sphingomyelin synthase; sphingomyelinase.

MeSH terms

  • Adipose Tissue / metabolism
  • Cardiovascular Diseases* / genetics
  • Cardiovascular Diseases* / metabolism
  • Ceramides / metabolism
  • Coronary Artery Disease* / genetics
  • Coronary Artery Disease* / metabolism
  • Humans
  • Pericardium / metabolism
  • Subcutaneous Fat / metabolism

Substances

  • Ceramides