The Effect of Age on the Expression of Ceramide-Metabolizing Enzymes in the Adipose Tissue of Patients with Coronary Artery Disease

Aim. To identify the features of gene expression of de novo synthesis enzymes and ceramide (Cer) degradation enzymes in fat depots of various localization in patients with cardiovascular diseases, depending on age.

Design. A single-center prospective clinical study.

Materials and methods. 60 patients with coronary artery disease (CAD) were examined. Biopsies of subcutaneous (SAT), epicardial (EAT), and perivascular adipose tissue (PVAT) were obtained during coronary bypass surgery. Gene expression of de novo Cer synthesis enzymes (C1 and C2 subunits of serine palmitoyltransferase — SPTLC1, SPTLC2; ceramide synthase 1–6 — CERS1–6; dihydroceramide desaturase — DEGS1) and degradation of Cer (acid ceramidase — ASAH1, sphingomyelin synthase 1 and 2 — SGMS1 and SGMS2,) were evaluated using quantitative polymerase chain reaction.

Results. The expression of Cer de novo synthesis enzyme genes is maximal in the ventricular tract of persons 75 years and older, with a high level of CERS5 and CERS6 (producing Cer14:0 and Cer16:0) in EAT — in persons 60–74 years old. The highest expression of the CERS2 gene (synthesizing Cer 20:0, 22:0, 24:0, 24:1, 26:0) in EAT, it was observed in the group of people aged 60–74 years, in PVAT — 75 years and older. Increased expression of the ASAH1 gene (degradation of Cer to sphingosine and free fatty acids) was detected in patients 75 years and older, SGMS1 and SGMS2 genes (conversion of Cer to sphingomyelin) — in persons 60–74 years of age in all AT. These results indicate the modulation of synthesis and accumulation of Cer in the AT ventricular localization with age.

Conclusion. The AT of patients with coronary heart disease differed in the level of expression of de novo synthesis enzyme genes and Cer degradation depending on age. It is likely that the AT ventricular localization undergoes deeper age-related remodeling, which can lead to the accumulation of Cer in the EAT and PVAT.

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