Test-system for inhibitors of inflammation at initial stages of ischemia and atherosclerosisстатья

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Дата последнего поиска статьи во внешних источниках: 29 мая 2015 г.

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[1] Test-system for inhibitors of inflammation at initial stages of ischemia and atherosclerosis / D. Aleksandrov, M. Pushkareva, S. Galkina, G. Sudina // FEBS Journal. — 2006. — Vol. 273, no. Supplement 1. — P. 212–212. It is commonly observed that inflammation is a permanent concomitant of atherosclerosis. Despite of different views onto atherosclerosis origination there are good evidences that one of the most important stages is endothelium dysfunction. Cholesterol deposition, macrophage invasion, lipoprotein oxidation and leukocyte adhesion lead to endothelium lesions and restriction of blood flow. 5-lipoxygenase in activated polymorphonuclear leukocytes (PMNL) and monocytes starts to synthesize leukotrienes (LT), witch are inflammatory chemoattractants. This process stimulates further migration of macrophages, PMNL and platelets. Leukocyte stimulation results also in so-called “respiratory burst” – rapid production of reactive oxygen intermediates (ROI), i.g. superoxyde-anion-radical. This oxidative product can effectively damage endothelium layer and, at least, destroy its integrity at many sites. Endothelial injuries lead to denudation of extracellular matrix proteins such as collagen and fibronectin. All these events are ordinary during different types of atherogenesis, such as ischemia, but also take place under asthma and some other diseases. Here we present a novel test-system for inhibitors of LT synthesis, ROI production and PMNL/endothelial cells (human umbilical vein endothelial cells) and PMNL/collagen adhesion. Such a wide scope provides us with a possibility to estimate the effect of potential medicine compounds on many cellular functions, which is important for evaluation of side-effects of tested compounds. Importantly, using this way we can get a lot of different parameters not only in complicated multifactor system but as well in several simple single-cell type assays, what is dramatically important for optimization of already existent inhibitors. All in all presented approach allows us to take into account the levels of endogenous pro-inflammatory agents and to evaluate the effects of newly synthesized molecular inhibitors. The results obtained using such system have confirmed its advances and revealed unknown functions of the natural substances like cholesterol sulfate (unpublished data) and sulfated galactocerebrosides. We propose this test-system to be a promising approach in further investigations of atherogenesis and drug development.

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