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.

Effect of Dan-Lou tablets on coronary heart disease revealed by microarray analysis integrated with molecular mechanism studies

“…Here we found that DLT decreased the expression level of EGFR in the myocardium of CHD rats, which may reduce cellular proliferation and differentiation. STAT5B, a member of the STATs protein family, is mainly involved in immune–inflammatory reactions and regulates cell proliferation, differentiation, and apoptosis [ 28 ]. Studies have shown that active STAT5B can activate the differentiation and generation of adipocytes through the mediation of peroxisome proliferator-activated receptor γ [ 29 , 30 ], thereby slowing the blood flow rate and accelerating plaque formation.…”

Relationship between the expression of angiotensin II receptors type 1 and vasoactive regulators in arterial hypertension

“…Исследование проводили с использованием реагентов фирмы BenderMedSystems (Австрия). Забор крови для исследования проводили натощак в утренние часы [8].…”

“…В прогрессировании АГ также немаловажное значение имеет нарушение межклеточных эндотелиальных взаимодействий, опосредованных VE-кадгерином, провоспалительная активация эндотелиоцитов, сопровождающаяся повышением экспрессии молекул адгезии, в частности, ICAM-1, VCAM-1, Е-селектина и т.п. [5][6][7][8][9]. Показано, что провоспалительная активация эндотелия, а также иммунокомпетентных клеток периферической крови поддерживается компонентами РААС, в частности АТ II, что также определяется активацией AT1R и опосредуется внутриклеточной активацией G-белков [10,11].…”