The role of AMPK protein kinase and individual components of the MAPK/SAPK signaling pathway in the regulation of vasoactive mechanisms in patients with arterial hypertension

Abstract

Introduction. The functional state of immunocompetent cells (ICC) plays an important role in the regulation of vasoactive mechanisms in patients with arterial hypertension (AH). In turn, an important role in the regulation of ICC metabolism plays an intracellular molecular sensor, adenosine monophosphate-dependent protein kinase (AMPK), which controls numerous intracellular processes as well as the production of biologically active molecules by cells depending on their energy balance. Aim: to assess the relationship between the content of AMPK protein kinase in MNCs and the state of the MAPK/SAPK signaling pathway as well as the level of vasoactive molecules and immunoregulatory factors in patients with hypertension. Materials and methods. We examined 55 patients of both sexes aged 47–67 years with primary hypertension with average and high cardiovascular risk. The control group consisted of 15 practically healthy individuals with normal blood pressure. The study material was venous blood samples taken from patients on the day of hospitalization. Results. The high level of protein kinase AMPK in the MNCs of patients with hypertension compared to the low level was associated with an increase in the production of prostaglandin E2, NO, and IL-4. An increase of eNOS, p38MAPK protein kinase, and HSP90 content was observed in MNCs. Along with this, there was a decrease in the production of proIL-1, IL-18, the soluble form of CD40L, and the content of protein kinase JNK, p70-S6K1, HSP70, and iNOS in MNCs. Conclusions. The high content of AMPK protein kinase in MNCs helps to reduce their pro-inflammatory activation, stimulates the production of NO, limits the activity of p38MAPK and JNK-dependent signaling pathways, promoting the normalization of the intracellular level of eNOS, HSP90 and the production of proinflammatory cytokines.