[Adiponectin gene expression in local fat depots in patients with coronary heart disease depending on the degree of coronary lesion].

AIM: To determine the dependence of adiponectin gene expression by subcutaneous, epicardial and perivascular adipocytes on the degree of coronary lesion in coronary heart disease. MATERIALS AND METHODS: 84 patients with coronary artery disease were examined. Of these, 39 people showed a moderate degree of atherosclerotic lesion of the coronary bed (less than or equal to 22 points) on the SYNTAX Score scale, 20 severe (2231 points), and 25 extremely severe (more than 32 points). Upon admission to the hospital, all patients underwent an echocardiographic study (Echocardiography, Acuson, Germany) with the calculation of the ejection fraction (EF) of the left ventricle (LV) to assess its systolic function. During a planned surgical intervention (coronary bypass surgery, CABG), adipocytes of subcutaneous, epicardial (EAT) and perivascular adipose tissue (PVAT) were taken. Adiponectin gene expression was evaluated by polymerase chain reaction (real-time PCR) using TaqMan probes. Statistical analysis was performed using Statistica 9.0. RESULTS: The maximum level of adiponectin expression was detected in adipocytes of PVAT, and the minimum EAT. With an increase in the degree of atherosclerotic lesion of the coronary bed, the expression of the adiponectin gene in adipocytes of local depots significantly decreases r=-0.82; p=0.023. Moreover, the low level of gene expression in EAT correlated with a decrease in LV EF by r=0.73; p=0.03. In adipocytes of subcutaneous and especially PVAT, gene expression was the highest in patients with a moderate degree of coronary lesion. CONCLUSIONS: Low adiponectin gene expression in EAT is associated with an increase in the degree of atherosclerotic lesion of the coronary bed and a decrease in LV EF.

[Genotoxic stress leads to the proinflammatory response of endothelial cells: an in vitro study]. / Genotoksicheskii stress vyzyvaet formirovanie éndotelial'nymi kletkami provospalitel'nogo fenotipa: issledovanie in vitro.

It was shown, that genotoxic stress can trigger endothelial disfunction and atherosclerosis, but the molecular genetic mechanisms of this process are poorly investigated. At the same time, inflammation also plays the important role in atherogenesis. This study aimed access of inflammatory marker expression in the endothelial cells exposed to alkylating mutagen mitomycin C (MMC). Primary human coronary (HCAEC) and internal thoracic artery endothelial cells (HITAEC) exposed to 500 ng/ml MMC (experimental group) and 0.9% NaCl (control) were used in this research. A gene expression profile was evaluated by quantitative reverse transcription PCR after 6 h exposure of endothelial cells to MMC (or 0.9% NaCl) followed by subsequent 24 h incubation in the mutagen-free cell growth media. The cytokine profile of endotheliocytes was studied by dot blotting. We found that MIF, IL-8, MCP-1, IP-10 and PDGFB were upregulated both in HCAEC and HITAEC, while MIP-1ß release remained unchanged. TIMP-2 was upregulated in HCAEC but not in HITAEC. sTNF RI was expressed only in HCAEC. According to gene expression analysis, HCAEC exposed to MMC are characterized by the increased mRNA level of IL-8, MCP-1 and IP-10; decreased expression of TIMP-2 and no differences in the expression of MIF, MIP-1ß and PDGFB compared to the control. In HITAEC, increased mRNA level of IL-8 and IP-10; decreased expression of MIF and TIMP-2, no differences in the expression of MCP-1, MIP-1ß and PDGFB was shown. TNF-RI expression was not detected in both cell lines. Thus, genotoxic stress in endothelial cells induced by MMC leads to differential inflammatory response that can trigger endothelial dysfunction.