Tag Archives: eNOS

Indexes of nitric oxide system in experimental antiphospholipid syndrome

O. Z. Yaremchuk, K. A. Posokhova, І. P. Kuzmak,
M. I. Kulitska, I. М. Klishch, M. M. Korda

I. Horbachevsky Ternopil National Medical University, Ukraine;
e-mail: yaremchuk@tdmu.edu.ua

Received: 11 November 2019; Accepted: 21 January 2020

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antibo­dies to negatively charged membrane phospholipids (aPL).  Endothelial dysfunction is one of the most dangerous­ APS manifestations followed by thrombosis, placental insufficiency and often foetal death due to circulatory disorders in placenta blood vessels. It is established that synthesis and bioavailability of nitric oxide (NO) in the endothelium are impaired at APS, but the role of NO system in pregnancy failure at this pathology remains ambiguous. The aim of this research was to estimate the indexes of the nitric oxide system in animals with an experimental antiphospholipid syndrome before pregnancy and on the 18th day of pregnancy, without­ treatment and under treatment with nitric oxide synthesis modulators (L-arginine and aminoguanidine). In the blood serum and liver of the BALB/c mice with experimental APS, the content of eNOS and iNOS by ELISA and the level of NO2 and NO3 with the use of Gris reagent were determined before pregnancy and on the 18th day of pregnancy. The data obtained indicate the relative inefficient NO production by eNOS and NO hyperproduction by iNOS in the blood serum and liver of mice in the pathogenesis of experimental APS. Thus, in mice with APS before pregnancy and on the 18th day of the pregnancy, the eNOS content and NO2 level were decreased while the iNOS content and NO3 level were increased compared to the indexes in the control animal group. L-arginine administration to the animals with APS at the follow-up periods resulted in an increased eNOS content and NO2, NO3 levels in blood serum and liver with the simultaneous decrease in iNOS content in the liver as compared to indexes in untreated mice with APS. The combined use of L-arginine and selective iNOS inhibitor aminoguanidine caused a significant increase in eNOS content and a decrease in iNOS content followed by normalization of NO2 and NO3 levels in blood and liver of mice with  experimental APS before pregnancy and on the 18th day of pregnancy compared to untreated mice with APS.

The mechanism of VEGF-mediated endothelial cells survival and proliferation in conditions of unfed-culture

T. V. Nikolaienko, V. V. Nikulina, D. V. Shelest, L. V. Garmanchuk

Educational and Scientific Centre “Institute of Biology”,
Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: nikolaenkotetiana@yandex.ua

The mechanisms of VEGF-mediated effects on endothelial cells during cancer development and progression is not clear. In present study the biological effects of VEGF, VEGF-rich culture medium of peritoneal macrophages from mice with Lewis lung carcinoma were studied on MAEC cell line under conditions of unfed culture. We have shown that VEGF increased cell proliferation by the 5th day of culturing vs control and anti-VEGF-treated cells. This effect was associated with increased consumption of glucose and NO production by the 2nd day while decreased – on the 5th day of cell culturing. VEGF-mediated NO production was dependent on Ca2+ ions. Block of Ca2+-channels (LaCl3) had more pronounced inhibitory effect vs chelator of Ca2+ ions (EDTA).  It was shown that peritoneal macrophages are the main suppliers of VEGF at tumor angiogenesis, as evidenced by the data obtained on model system of endothelial cells synchronized in G0/G1 phase.