RELATIONSHIP OF EXPRESSION OF CERAMIDE SYNTHESIS ENZIES DE NOVO WITH GENDER AND AGE IN CORONARY HEART DISEASE

Abstract

Introduction. Adipose tissue (AT) is a potential source of ceramides. Of particular interest is the expression of de novo ceramide synthesis enzymes in the AT of the heart and blood vessels localized in close proximity to the lesion. Male gender and age are considered to be one of the main risk factors for coronary heart disease (CHD).Purpose: to study the relationship between the expression of de novo ceramide synthesis enzymes in adipose tissue (AT) and non-modifiable risk factors for cardiovascular disease (CVD) in coronary heart disease (CHD).Materials and methods. The study included 30 patients with coronary artery disease who underwent coronary artery bypass grafting. During the operation, biopsies of subcutaneous, epicardial, perivascular VT (SVT, EAT, PVAT, respectively) were obtained. Expression of genes for de novo ceramide synthesis enzymes (subunits of serine palmitoyltransferases C1 and C2 SPTLC1, SPTLC2; ceramide synthase 1-6 CERS1-6; dihydroceramide desaturase DEGS1) was assessed by quantitative real-time PCR. Statistical analysis of the results was performed using GraphPad Prism 8 (GraphPad Software).Results. Men with CAD were characterized by a higher level of expression of de novo ceramide synthesis enzymes SPTLC1, CERS1, 5 and DEGS1 in EAT and PVAT than women. The expression of the studied enzymes in SAT did not differ significantly depending on gender. In patients older than 60 years, the maximum expression levels of SPTLC1, CERS1,2,6, DEGS1 were found in cardiac VT compared with patients younger than 50 years and 50-59 years (p<0.005). Correlation analysis revealed a direct dependence of the mRNA level of SPTLC1, CERS1,2,6, DEGS1 in EAT and PVAT with age (p<0.05). Correlation analysis showed a direct relationship between age and gene expression levels of the following enzymes: CERS1 in EAT and PVAT (r=0.60, p=0.027 and r=0.51, p=0.02), CERS2 in PVAT (r=0, 69, p=0.013), CERS5 in EAT (r=0.57, p=0.011), DEGS1 in EAT (r=0.66, p=0.043). Attention is drawn to the increased expression of genes for key enzymes of de novo ceramide biosynthesis in cardiac VT in patients with coronary artery disease aged 50–59 years and PVAT in patients older than 60 years, which does not contradict the generally accepted opinion about an increase in ceramide production with age. Using logistic regression analysis, it was shown that the presence of CVD risk factors is associated with an increase in the expression of de novo ceramide biosynthesis enzymes in patients with CAD. Thus, male sex is associated with an increase in SPTLC1 expression in EAT (OR=1.72, 95% CI 1.17-1.94, p=0.013) and PVAT (OR=1.21, 95% CI 1.03-1 .52, p=0.032), as well as CERS1 and DEGS1 in EAT (OR=1.55, 95% CI 1.13-1.83, p=0.024 and OR=1.31, 95% CI 1.07- 1.64, p=0.041, respectively). The age of patients is associated with increased expression of CERS2 in EAT (OR=1.43, 95% CI 1.07-1.71, p=0.004) and DEGS1 in PVAT (OR=1.50, 95% CI 1.12-1 .83, p=0.002).Conclusion. Close relationships were found between the expression of enzymes of the main ceramide synthesis pathway in VT of cardiac localization and gender and age characteristics of patients with coronary artery disease. Determination of the expression of de novo ceramide biosynthesis enzymes plays an important role for risk stratification both in addition to traditional risk factors and independently, which is important for primary and secondary prevention of CVD.

Keywords

• ишемическая болезнь сердца
• риск сердечно-сосудистых заболеваний
• экспрессия ферментов синтеза церамидов