Relationships between the expression of adipocytokine genes and the calcification of coronary arteries in patients with coronary artery disease

Abstract

Dysfunctional changes and remodeling of adipose tissue (АT) are associated with the formation of microcalcifications in the vascular wall. Biologically active substances synthesized by АT (adipocytokines) can act as promoters and inhibitors of vascular calcification development. The few available experimental and clinical studies do not fully explain the possible mechanisms of these effects.Aim. To study the relationships between the adipocytokine profiles of adipocytes in epicardial and perivascular AT with the severity of coronary artery calcification in patients with coronary artery disease (CAD).Material and Methods. A total of 125 patients with CAD aged 59 (53; 66) years were examined. The isolated adipocytes of subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT), and perivascular adipose tissue (PVAT), obtained during coronary artery bypass grafting, were used to determine gene expression and secretion of adipocytokines (adiponectin, leptin, and IL-6). Expression of adipocytokine genes was assessed using quantitative PCR with detection of products in real time (real-time qPCR); the concentration of adipocytokines in the culture medium was determined by enzyme-linked immunosorbent assay using R&D Systems kits (Canada). Coronary artery (CA) calcification degree was assessed by multislice spiral computed tomography (MSCT) method. The calcium index of CA was determined by the Agatston method using the Syngo Calcium Scoring software package (Siemens AG Medical Solution, Germany).Results. Massive coronary calcification (CC) had the highest prevalence (58.8%) in patients with CAD. The highest level of expression of the ADIPOQ gene in all types of fat stores was observed in patients with moderate/medium CС compared to those with massive CС; the maximum expression of ADIPOQ was observed in the culture of PVAT adipocytes. Expression of the LEP and IL6 genes in massive CC was higher, with the maximum values in the culture of EAT adipocytes relative to SAT and PVAT adipocytes. Decreases in the levels of ADIPOQ mRNA and its secretion, increases in the levels of mRNA of LEP and IL6 and their secretion in adipocytes of the EAT and PVAT were associated with the development of СС in patients with CAD.Conclusion. Proinflammatory adipokines produced by adipocytes of patients with CAD during hypoxia induced vascular calcification by stimulating oxidative stress, osteoblast differentiation, apoptosis, and proliferation of smooth muscle cells. Endothelial cells, when stimulated with proinflammatory adipocytokines, tended to transform into osteoblasts, which further aggravated the degree of vascular inflammation and calcification.