Search

The therapeutic effect of mitochondria-targeted antioxidant 10-(6´-plastoquinonyl)decyltriphenylphosphonium bromide (SkQ1) in experimental models of acute inflammation and wound repair has been shown earlier. It was suggested that the antiinflammatory activity of SkQ1 is related to its ability to suppress inflammatory activation of the vascular endothelium and neutrophil migration into tissues. Here, we demonstrated that SkQ1 inhibits activation of mast cells (MCs) followed by their degranulation and histamine release in vivo and in vitro. Intraperitoneal injections of SkQ1 in the mouse air-pouch model reduced the number of leukocytes in the air-pouch cavity and significantly decreased the histamine content in it, as well as suppressing MC degranulation in the air-pouch tissue. The direct effect of SkQ1 on MCs was studied in vitro in the rat basophilic leukemia RBL-2H3 cell line. SkQ1 inhibited induced degranulation of RBL-2H3 cells. These results suggest that mitochondrial reactive oxygen species are involved in the activation of MCs. It is known that MCs play a crucial role in regulation of vascular permeability by secreting histamine. Suppression of MC degranulation by SkQ1 might be a significant factor in the antiinflammatory activity of this mitochondria-targeted antioxidant.

Using blood monocytes and lymphocytes from atherosclerotic patients and healthy subjects we have investigated activity of GM3 synthase, cellular levels of ganglioside GM3 and its role in monocyte adhesion to cultured human umbilical vein endothelial cells (HUVEC). The results showed that activity of GM3 synthase and cellular levels of ganglioside GM3 in blood mononuclear cells from atherosclerotic patients were several-fold higher than those from healthy subjects. In monocytes the activity of GM3 synthase was one an order of magnitude higher than in lymphocytes from both groups studied; this suggests the major contribution of monocytes to enhanced biosynthesis and levels of GM3 in mononuclear cells in atherosclerosis. Enrichment of monocytes from healthy subjects with ganglioside GM3 by incubation in medium containing this ganglioside increased adherence of these monocytes to HUVEC up to the values typical for monocytes from atherosclerotic patients. In addition, an increase in CD1 1b integrin expression was observed that was comparable to that seen in lipopolysaccharide-activated monocytes. It is suggested that in atherosclerosis the enhanced cellular levels of GM3 in monocytes and lymphocytes may be an important element of cell activation that facilitates their adhesion to endothelial cells and penetration into intima.

Today there exists a wide variety of laboratory and instrumental methods aimed at diagnosing an unstable carotid aortosclerotic plaque. Assessment of the laboratory indices is not sufficiently effective since it does not allow of revealing the fact of the formation of an unstable plague at early stages and to determine its localization. The instrumental methods employed (ultrasonographic study, magnetic resonance imaging, multiplanar computed tomography, positron emission tomography) were focussed on detecting pathomorphological markers of instability - thickness of the fibrous coating, structural plaques, the presence of erosions, ulcerations, haemorrhages, calcifications, lipid nucleus, activity of the cellular processes inside the plaque. The revealed signs promote early diagnosis of unstable atherosclerotic plaque with the determination of its localization. Nevertheless, they do not provide evidence about the danger of its rupture, whereas the overwhelming majority of acute vascular catastrophes including acute impairments of cerebral circulation is directly associated with arterial thrombosis resulting from rupture of the atherosclerotic plaque. Therefore, search for new methods aimed at prediction of complications of the atherosclerotic plaque which would be employed in routine clinical practice still remain urgently important today. The most promising is the study of the state of the atherosclerotic plaques of carotid arteries for prediction of acute impairment of cerebral circulation.

A complex histomorphometric and clinical-instrumental analysis of atherosclerotic lesions of the carotid arteries obtained during carotid endarterectomies (CEE) of patients with hemodynamically significant stenoses was conducted. Two groups of patients were compared: symptomatic, which earlier underwent cerebral vascular accident (CVA) or transitory ischemic attacks (TIA), and asymptomatic ones with no complications of the disease. Statistical analysis of clinical and laboratory data showed no significant differences between two groups except for the level of lipoprotein(a) [Lp(a)] in the blood plasma, which was higher (p<0.05) in asymptomatic patients compared with symptomatic ones. Statistical analysis of carotid arteries ultrasound duplex scanning (USDS) in the preoperative period did not reveal significant differences in the degree of maximum vessels stenosis between the compared groups of patients. Surface defects of atherosclerotic plaques (ASP) were shown to be significantly more common (p<0.05) in the group of symptomatic patients compared with asymptomatic ones. According to histological analysis 88% of extracted ASP was unstable in symptomatic patients and 77% of ASP - in asymptomatic patients. This may indicate high risk of CVA/TIA in both groups of patients. Statistical evaluation of magnetic resonance tomography (MRT) and USDS techniques in comparison with abilities of the most reliable histological analysis showed that both non-invasive diagnostic methods are highly sensitive in detecting unstable ASP, though MRT showed higher level of specificity compared with USDS.