[Comparison of morphological features of carotid arteries atherosclerotic plaques with clinical-instrumental data in symptomatic and asymptomatic patients with severe carotid atherosclerosis].

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.

[Comparative transcriptome analysis of human aorta atherosclerotic lesions and peripheral blood leukocytes from essential hypertension patients].

One of the major cardiovascular risk factor which predisposes to and accelerates atherosclerosis is arterial hypertension (AH). To determine the molecular basis of the crosslink between AH and atherosclerosis for the development of new treatment strategies large-scale transcriptome analysis of the cells implicated in atherogenesis is needed. We used cDNA microarray technique for simultaneous analysis of gene expression in human abdominal aorta normal sites and atherosclerotic lesions of different histological types, as well as in peripheral blood leukocytes from patients with essential hypertension (EH) and donors. The microarray data were verified by quantitative RT-PCR (reverse transcription coupled with polymerase chain reaction) and immunohistochemical analysis. Differential expression of 40 genes has been found, among which twenty two genes demonstrated up-regulation and 18 genes demonstrated down-regulation in atherosclerotic aorta compared with normal vessel. New gene-candidates, implicated in atherogenesis, have been identified - FPRL2, CD37, CD53, RGS1, LCP1, SPI1, CTSA, EPAS1, FHL1, GEM, RHOB, SPARCL1, ITGA8, PLN, and COL14A1. These genes participate in cell migration and adhesion, phenotypic changes of smooth muscle cells, immune and inflammatory reactions, oxidative processes and extracellular matrix remodeling. We have found increased expression levels of CD53, SPI1, FPRL2, SPP1, CTSD, ACP5, LCP1, CTSA and LIPA genes in peripheral blood leukocytes from EH patients and in atherosclerotic lesions of human aorta. The majority of these genes significantly (p<0.005) positively (r>0.5) correlated with AH stage as well as with histological grading of atherosclerotic lesions.

[Detection of bone marrow-derived cells in neointimal thickening in the rat carotid artery by nested polymerase chain reaction].

The bone marrow origin of cells involved in neointimal formation after injury of the luminal surface of the vessel was confirmed by highly sensitive nested polymerase chain reaction on isolated vascular wall cells. The model of intimal hyperplasia after balloon angioplasty of the carotid artery in radiation bone marrow chimeras between male and female Wistar rats was used. The Y chromosomes of rat male donors of the bone marrow for irradiated females were used as a marker of bone marrow-derived cells. This approach demonstrated a bone marrow origin of a large fraction of alpha-actin-positive (smooth muscle) neointimal cells.

[Expression of urokinase plasminogen activator, its receptor and plasminogen activator inhibitor type 1 in different types of atherosclerotic lesion in human aorta]. / Ekspressiia urokinazy, ee retseptora i ingibitora aktivatorov plazminogena 1-go tipa v stenke aorty cheloveka pri raznykh tipakh ateroskleroticheskogo porazheniia.

The role of plasminogen activators in the regulation of key processes of atherosclerosis progression stays unclear. The aim of this study was to evaluate the expression of urokinase plasminogen activator (uPA), its receptor (uPAR) and the plasminogen activator inhibitor type 1 (PAI-1) in human aorta, and to balance them with the stage of atherosclerotic lesion. We have shown that uPA and uPAR in normal aorta are mostly expressed by intimal smooth muscle cells. The expression of these proteins was up-regulated in diseased aorta compared to normal artery. The most part of cells in both fatty streak and fibro-fatty lesion were monocytes/macrophages, and about 60% of these cells expressed uPA and its receptor. PAI-1 was mostly localized on the lumonal part of the aorta and in the extracellular matrix of the intima. We observed a moderate increase of PAI-1 expression in atherosclerotic lesion. Thus, our data indicate participation of plasminogen system in atherogenesis.

[A new concept of development of neointimal hyperplasia]. / Novaia kontseptsiia razvitiia giperplazii intimy sosudov.

The intima hyperplasia is a major morphological feature of various arterial pathologies such as atherosclerosis, postangioplasty restenosis and transplantation arteriopathy. It is commonly assumed that smooth muscle cells (SMC) comprising loci of the intima hyperplasia originate from arterial media. However, recent studies suggest that the bone marrow could also supply circulating vascular progenitor of SMCs and endothelial cells (EC). Such bone marrow progenitors participate in the formation of a cellular mass of neointima after experimental allotransplantation, mechanical vessel injury or hyperlipidemia induced experimental atherosclerosis. Circulating SMC and EC progenitors are also likely to be involved in the transplantation arteriopathy development in humans but their roles in the atherosclerosis and restenosis remain to be determined. Stages of the mobilization, defferentiation and proliferation of SMC progenitors could provide point of attack for new therapeutic strategies for the treatment of proliferative vascular diseases. The precise understanding of the neointima cells origin could provide a key for development of the optimal therapeutic strategy of treatnent of such disorders. This review is focused on the pathological significance of circulating progenitors of the bone marrow origin, particularly on the SMC progenitors, for development of vascular wall disorders.

[Expression, regulation, and pathophysiological role of NAD(P)H oxidases in atherogenesis]. / ékspressiia, reguliatsiia i rol' NAD(P)H-zavisimykh oksidaz v aterogeneze.

Oxidative stress has been implicated in the development and progression of atherosclerotic lesions. Significant increase of reactive oxygen species production by vascular cells can lead to progression of atherosclerotic lesions and development of unstable plaques due to triggering the apoptosis of endothelial and smooth muscle cells, expression of matrix metalloproteases and inflammatory cytokines. Cytolysis NAD(P)H-dependent oxidases appeared to be involved in reactive oxygen species production in the vascular network. Understanding of functions and regulation of individual NAD(P)H oxidases in atherosclerotic lesions can facilitate the development of novel therapeutic strategy for treating atherosclerosis. This review summarizes current data regarding expression, regulation and pathophysiological significance of these enzymes during development and progression of human atherosclerotic lesions.

[The origin of neointimal cells in the rat carotid artery after balloon angioplasty]. / Proiskhozhdenie kletok neointimy, obrazovannoi v sonnykh arteriiakh krys, posle ballonnoi angioplastiki.

At present the issue of a possible role of circulating stem cells and precursors in pathological vascular wall remodeling after angioplasty remains unsolved. Therefore the origin of neointimal cells was examined in the rat carotid artery after balloon angioplasty using morphological and immunocytochemical approaches. It is shown that at the early stages (1-7 days) after vessel injury acute inflammatory response arises in the arterial wall recruiting neutrophils, monocytes, macrophages as well as large amounts of low-differentiated blood-derived cells. At the late stages (10-28 days), at the area of injured intima, a new hyperplastic intima (neointima) is formed, which consists of cells carrying specific smooth muscle markers--alpha-actin and smoothelin. The study on cell proliferative behaviour in the injured vessel wall by bromodeoxyuridine showed that in the process of neointima formation blood-born rather than resident cells are involved. Probably, early smooth muscle and endothelial precursor cells penetrate into injured area with blood stream, where they proliferative and differentiate into mature cells.

[Expression of T-cadherin in the rat carotid artery wall after balloon injury and in different rat organs]. / Ekspressiia T-kadgerina v razlichnykh organakh, a takzhe v stenke sonnykh arterii pri ballonnom povrezhdenii u krys.

T-cadherin is an unusual glycosilphosphatidylinositol (GPI)-anchored member of the cadherin family of cell adhesion proteins. In contrast to classical cadherins, tissue distribution of T-cadherin so far remained unknown. We examined tissue distribution of T-cadherin in rats using Western blotting and immunohistochemical method. Our results show that T-cadherin is expressed in all types of muscles (cardiac, striated, and smooth muscles), in brain neurons, and spinal cord, in the vessel endothelium, at the apical pole of intestinal villar epithelium, in the basal layer of skin, and eosophagal epithelium. Blood-derived and lymphoid cells as well as connective tissue were T-cadherin-negative. The highest level of T-cadherin expression was revealed in the cardiovascular system. Although T-cadherin was detected in smooth muscle cells, its role in the intimal thickening and restenosis is not known. We examined T-cadherin expression within 1-28 days after balloon injury of rat left carotid arteries. T-cadherin expression was valued immunohistochemically with semiquantitative method. In uninjured arteries, T-cadherin was expressed in endothelial (vWF-positive) cells, and smooth muscle (alpha-actin-positive) cells (SMCs). After denudation of arterial wall, T-cadherin was present both in the media and neointima. We revealed dynamics of T-cadherin expression in the media of injured artery: an essential increase being registered at the stage of cell migration and proliferation in the media and neointima (1-7 days), followed by its decrease to the baseline level (10-28 days). The high upregulation of T-cadherin expression in the media and neointima during migration and proliferation of vascular cells after vessel injury enables us to suggest the involvement of T-cadherin in vessel remodeling after balloon catheter injury.

[Effect of x-irradiation on amoebocytopoiesis in the snail]. / Issledovanie vliianiia rentgenovskogo oblucheniia na amebotsitopoéz u vingradnoi ulitki.

The [3H]thymidine radioautography technique was used to study the objective laws of the renewal of blood cells (amoebocytes) of the edible snail (Helix pomatia) after X-radiation. Cells which are the precursors of amoebocytes actively proliferating beyond the limits of peripheral blood have been shown to possess a high radiosensitivity. The action of lethal doses of radiation (200-500 Gr) suppresses their proliferation and leads to the irreversible amoebocytopenia. Radioresistant cells lost the ability to the proliferation circulate in the peripheral blood.