[PROINFLAMMATORY CYTOKINES AND SIGNALING PATHWAYS IN PERIPHERAL BLOOD MONONUCLEAR CELLS IN PATIENTS WITH CORONARY ARTERY DISEASE].

Abstract

Aim: To determine content of mononuclear ells (MNC) in peripheral blood of patients with coronary heart disease (CHD) and factors responsible for their functional state and cytokine production.

Materials and methods: Concentration of proteinkinases JNK1/2, ERK1/2, MAPK38, AKT1, JAK2, FAK, AMPK, p70S6K, STAT3, STAT5B and STAT6 was determined in MNC lysate by immune-enzyme assay. Interleukin 1β, 2, 4 and y-interferon levels were measured in blood sera.

Results: In patients with angina of effort and unstable angina, the JNK level was 59,8% and 53,1% higher than the normal one respectively (р=0,013) and (р=0,012). The level of the nuclear transcription factor was 26,9% (р=0,015) and 27,9% (р=0,017), JAK2 31,5% (р=0,022) and 48,6% (р=0,018), STAT3 49,6% (р=0,025) and 55,3% (р=0,02), STAT5B 21,5% (р=0,018) and 30,2% (р=0,011) lower. These changes were associated with a 13,1% (р=0,047) and 51,4% (р=0,019) rise in the STAT6 level, 30,1% (р=0,025) and 79,4% (р=0,003) FAK level, 7,6% (р=0,09) and 15,2% (р=0,039) АКТ1 level, 65,3 (р=0,02) and 76,2% (р=0,017) p70S6K level.

Conclusion: Results of the study suggest persistent pro-inflammatory activation of whole blood cells in CHD patients due to enhanced levels of IL-1 and IL-2, components of the MAPK/SAPK signal pathway in MNC and decreased STAT3 level determining cell sensitivity to IL-10. The elevated intracellular level of ERK and JNK us responsible for high responsiveness of MNC to pro-inflammatory cytokines.