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Biomedical subjects

Y V Bobryshev

Publications and source records attributed to Y V Bobryshev.

At least 37 records · Page 2Linked to original sources
PubMed2000

Dendritic cells and their involvement in atherosclerosis.

Dendritic cells constitute a unique family of cells able to induce primary immune responses. Over the past decade, immunologists have been increasingly preoccupied with dendritic cells and dendritic cells are now seen as a panacea for vaccine development, tumour immunotherapy and a host of other immunological applications. The recent finding of dendritic cells accumulating in atherosclerotic lesions should stimulate investigation of their contributions to atherogenesis and their potential use in anti-atherosclerosis therapies.

Animals↗
PubMed2000

Accumulation of lymphocytes, dendritic cells, and granulocytes in the aortic wall affected by Takayasu's disease.

The aim of this study was to analyze the cellular composition of the arterial wall in Takayasu's disease and to investigate the contribution of the various cell types to the immunoinflammatory processes and degenerative alterations of the vessel wall in this disease. Specimens of aorta were obtained at operation from 10 patients with Takayasu's arteritis. The duration of disease ranged from 2 months to 13 years. Immunohistochemical investigation was carried out using the antibodies CD3 (to identify T-cells), CD20 (B-cells), S-100 (dendritic cells), CD68 (macrophages), CD15 (granulocytes), von Willebrand factor (endothelial cells), and alpha-smooth muscle actin (smooth muscle cells). All specimens showed distinctive histologic features of Takayasu's arteritis and contained inflammatory infiltrates, but the degree of their accumulation within the aortic wall varied. Inflammatory infiltrates within the deep part of the intima, around areas of neovascularization and within the adventitia contained T-cells colocalizing with dendritic cells. Nodules formed by large numbers of intermingling T-cells and B-cells enriched with dendritic cells were observed in the adventitia. Massive accumulation of granulocytes and their destruction within the adventitia were prominent in all cases. This is the first study that establishes the presence of dendritic cells and granulocytes in Takayasu's disease. Dendritic cells are probably involved in the immunoinflammatory processes through their interaction with T-cells and B-cells. The present observations may help understanding of the pathogenesis of Takayasu's disease.

Adult↗
PubMed2000

Electron-microscopic detection of apoptotic and necrotic cell death in non-atherosclerotic areas of stenotic aortocoronary saphenous vein bypass grafts.

Aortocoronary saphenous vein bypass grafts undergo structural alterations within the arterialized vein, resulting in graft stenosis and failure. Areas of the acellular intima contribute to fissuring, cracking and ulceration, while areas of the media become highly vascular but thinned. This study aimed to examine the ultrastructural features of cell death, including apoptosis and necrosis, in non-atherosclerotic areas of the stenotic aortocoronary saphenous vein bypass grafts. Thirteen stenotic vein grafts were obtained at redo coronary artery bypass grafting. The ultrastructural features of cell death were analysed by electron microscopy. Typical features of necrosis, including focal areas of cytoplasmic oedema, plasmalemmal destruction and nuclear condensation with cytoplasmic organelle destruction, were observed throughout the intima and media. Features of apoptosis, including the presence of apoptotic bodies, were also identified in the hyperplastic intima and its adjacent media. Our observations suggest that both apoptosis and necrosis occur in non-atherosclerotic areas of stenotic aortocoronary saphenous vein bypass grafts.

Aged↗
PubMed1999

Neovascular expression of VE-cadherin in human atherosclerotic arteries and its relation to intimal inflammation.

OBJECTIVE: The present work aimed to investigate how the Ca(2+)-dependent cell adhesion molecule vascular endothelial (VE)-cadherin might be involved in atherogenesis. METHODS: Specimens of human carotid artery and aorta were obtained at operation. An immunohistochemical approach using cell-type specific antibodies examined how VE-cadherin expression in areas of neovascularisation related to the accumulation of immunocompetent and inflammatory cells within atherosclerotic plaque. Electron microscopy was used to examine the structural characteristics of neovessels and the cell composition in the surrounding intimal matrix. RESULTS: In all the non-atherosclerotic aortic segments, VE-cadherin expression was observed only in the adventitia and the outer third of the media. Within the atherosclerotic arterial segments, VE-cadherin was expressed in all layers of the arterial wall including the intima where VE-cadherin was expressed by endothelial cells in areas of neovascularization. In some neovessels, loss of VE-cadherin expression was associated with increased focal accumulation of T-cells, macrophages and dendritic cells. Electron-microscopic examination demonstrated varying degrees of endothelial continuity in the intimal neovessels. Within those neovessels which were surrounded by a large number of immunocompetent and inflammatory cells, some inter-endothelial cell contacts were open allowing the penetration of blood cells through patent intercellular zones. CONCLUSIONS: VE-cadherin is expressed in atherosclerotic lesions by endothelial cells associated with neovascularisation. Downregulation of VE-cadherin expression within some intimal neovessels is accompanied by increased entry of immunocompetent cells into the intimal matrix surrounding areas of neovascularization which suggests that disorganizing endothelial cell-to-cell interactions within neovessels is significant in atherogenesis.

Adult↗
PubMed1999

Accumulation of co-localised unesterified cholesterol and neutral lipids within vacuolised elastin fibres in athero-prone areas of the human aorta.

To investigate whether there are alterations of elastin fibres in the arterial intima at the pre-atherosclerotic stage, grossly normal areas of human thoracic aorta were taken soon after death from 13 healthy trauma victims whose ages ranged from 16 to 40 years. Two areas were compared: atherosclerosis-prone (AP) areas localised to the dorsal aspect of the aorta along the rows of intercostal branch origins, and atherosclerosis-resistant (AR) areas from the ventral aorta. Electron microscopic analysis combined with cytochemical staining was applied. Unesterified cholesterol was identified using the filipin-staining technique while neutral lipids were visualised by the OTO-technique. Intimal features were studied by combining the filipin-staining and the OTO-technique. Electron microscopical examination showed that in both AR and AP areas, some elastin fibres in the intima were vacuolised. Unesterified cholesterol was found to be predominantly localised in the musculoelastic layer, in particular, inside the vacuolised elastin fibres. This localisation was seen in all 13 AP areas studied in contrast to the AR areas where it was observed in only four of 13 aortas studied (P < 0.0005, chi2-test). Accumulation of neutral lipids inside vacuolised elastin fibres was found in five out of 13 AP areas but was not observed in any of the AR areas (P=0.01, chi2). A combination of the filipin-staining and OTO-techniques showed that some deposits of neutral lipids and unesterified cholesterol within vacuolised elastin fibres were independently located from each other, but more frequently, neutral lipids were co-located with unesterified cholesterol. The present observations indicate a difference between AP and AR intimal areas which, in particular, relates to the structure of elastin fibres in the musculoelastic layer. The observations suggest that alterations of the extracellular matrix are involved in the trapping and retention of cholesterol and neutral lipids within the intima at an early stage in the development of atherosclerotic lesions.

Adolescent↗
PubMed1999

Involvement of dendritic cells in long-term aortocoronary saphenous vein bypass graft failure.

Antigen-presenting dendritic cells are present in atherosclerotic lesions in human arterial intima, but have not been investigated in atherosclerotic and hyperplastic stenotic lesions that affect vein grafts used as arterial conduits. This study was undertaken to examine whether dendritic cells are present in aortocoronary artery saphenous vein bypass grafts affected by high-grade atheromatous stenosis. Stenotic saphenous vein coronary artery bypass grafts (angiographic luminal stenosis > 75%) were harvested from 10 patients (nine male, one female), aged 4271 years (mean 56.5) at re-do operation. The mean time interval from bypass surgery to the excision of stenotic grafts was 11.5 years (range 2-21). The specimens were fixed in 10% buffered formalin, embedded in paraffin blocks and the sections stained with antibodies to S-100 (to identify dendritic cells), CD3 (T cells), CD68 (macrophages), von Willebrand factor (endothelial cells) and alpha-smooth muscle actin (smooth muscle cells) using avidin-biotin complex immunoperoxidase technique. Normal veins were obtained during saphenous vein femoro-popliteal grafting. The stenotic venous grafts showed histological features typical of extensive arterialization, intimal hyperplasia, atherosclerotic plaque-like lesions, calcification and thrombosis. In areas of intimal hyperplasia, S-10O-positive cells were distributed irregularly among smooth muscle cells. S-100-positive dendritic cells were seen most frequently within atherosclerotic plaque-like lesions where they co-localized with CD3+ cells and CD68+ cells. S-100-positive dendritic cells were also seen accumulating within calcific foci. No S-100-positve cells were found in normal, ungrafted saphenous veins. We conclude that dendritic cells are present in aortocoronary saphenous vein bypass grafts affected by high grade stenosis. Dendritic cells are probably involved in immune mechanisms of atherogenesis through their interactions with T cells and macrophages. The accumulation of dendritic cells within calcific foci suggests their contribution to the calcification of stenotic venous grafts.

Adult↗
PubMed1999

Dendritic cells in venous pathologies.

Dendritic cells are potent antigen-presenting cells responsible for the activation of T-lymphocytes in various immune responses. Their role in the initiation of immune reactions in allergies, autoimmune diseases, tumors, transplantation, and, more recently, in atherosclerosis has been well established, but their involvement in venous pathologies has not been previously investigated. The aim of this study was to determine whether dendritic cells are present in veins affected by varicosity and thrombophlebitis. Three groups of veins obtained at operation were studied: (1) varicose veins of the great saphenous vein from patients who were undergoing vein stripping for primary varicosity; (2) segments of the great saphenous vein from patients with varicosity complicated by thrombophlebitis; and (3) great saphenous veins without varicosity or thrombophlebitis from patients who were undergoing femoropopliteal bypass grafting. The specimens were fixed in 10% neutral buffered formalin and embedded in paraffin, and the sections were stained with antibodies to S-100 (to identify dendritic cells), CD3 (T-lymphocytes), CD68 (macrophages), von Willebrand factor (endothelial cells), alpha-smooth muscle actin (smooth muscle cells), and CD15 (mast cells) by use of avidin-biotin complex (ABC) immunoperoxidase technique. Immunohistochemical examination showed that no S-100-positive dendritic cells were present in normal saphenous veins. In contrast, S-100-positive cells with dendritic cell morphology were detected in the intima and media of veins with varicosity and thrombophlebitis, where they represented a minor cell population. S-100-positive dendritic cells were located between smooth muscle cells as well as around areas of neovascularization where they colocalized with T-lymphocytes. The present work suggests that dendritic cells might be involved in pathological processes in veins affected by varicosity and thrombophlebitis. The authors speculate that dendritic cells may be involved in the inflammatory mechanisms in these veins through their interaction with T-lymphocytes.

Adult↗
PubMed1999

55-kD actin-bundling protein (p55) is a specific marker for identifying vascular dendritic cells.

Compared with other members of the dendritic cell family, the antigen profile of the recently recognized vascular dendritic cells has received limited attention. This study demonstrates that vascular dendritic cells in the human aorta and carotid arteries express 55-kD actin-bundling protein (p55), a specific marker for blood dendritic cells and Langerhans cells. This finding will facilitate screening of dendritic cells during their isolation from the arterial wall, as well as other investigations.(J Histochem Cytochem 47:1481-1486, 1999)

Actins↗
PubMed1999

Ultrastructural recognition of dendritic cells in the intimal lesions of aortas of chickens affected with Marek's disease.

The present study was undertaken to determine whether dendritic cells contributed to the intimal abnormalities seen in the aortas of chickens infected with Marek's disease. Semithin sections were used to select aortic segments in which the intima was thickened by lymphocytic infiltrates. Ultrathin sections were then examined. Intermingled with lymphocytes within the intimal thickenings were cells with an appearance typical of dendritic cells including long processes and a unique tubulovesicular system. In these cellular processes the tubulovesicular system was hypertrophied with the tubular cisterns characteristically forming concentric cyclical layers. Our observations show that dendritic cells are present in the aortic lesions of Marek's disease and are presumably involved in related immune mechanisms.

Animals↗
PubMed1999

Structural features of cell death in atherosclerotic lesions affecting long-term aortocoronary saphenous vein bypass grafts.

Aortocoronary saphenous vein bypass grafts fail because of structural pathologies (thrombosis, intimal hyperplasia and atherosclerosis) within the 'arterialized' vein leading to graft stenosis. This study examined structural characteristics of atherosclerotic alterations in long-term aortocoronary artery saphenous vein bypass grafts with particular attention to the features of cell death in atherosclerotic lesions. Stenotic vein grafts were obtained from 10 patients at redo coronary artery bypass grafting operations. All the grafts were affected by histological abnormalities, with eight out of ten grafts showing evidence of atherosclerotic alterations in the intimal hyperplastic layer. Areas containing foam cells were examined by electron microscopy. Cells with cytoplasmic lipid accumulations were characterized by varying degrees of chromatin condensation, fragmentation or dispersion, by focal areas of oedema and vacuolisation of their cytoplasm, and by plasmalemmal destruction. Some lipid-filled cells exhibiting signs of destruction contained myofilaments and basal membrane fragments, allowing them to be identified as smooth muscle cells. Macrophage foam cells were found to have undergone similar destruction. No cells showing nuclear degeneration were observed to have intact cytoplasmic organelles. Neither were apoptotic bodies identified, but necrotic remnants were frequently seen. The results suggest that cell death in atherosclerotic lesions affecting aortocoronary artery saphenous vein bypass grafts occurs through oncosis rather than by apoptosis.

Adult↗
PubMed1999

Ultrastructural identification of cells with dendritic cell appearance in atherosclerotic aorta of apolipoprotein E deficient mice.

The present electron microscopic study was undertaken to see whether cells with a dendritic cell appearance accumulate in atherosclerotic lesions of apolipoprotein E (apoE) deficient mice. Atherosclerotic aortas from 7 eight-month old apoE deficient mice were examined. In atherosclerotic plaques as well as in the underlying media and adventitia, cells with a dendritic cell appearance including the presence of a unique tubulovesicular system were detected. The tubulovesicular system was most hypertrophied in their cellular processes where the continuous cisterns sometimes formed circular structures. The cells containing the tubulovesicular system lacked lysosomes and phagolysosomes and their cytoplasm was free of lipid inclusions. The present observations suggest that dendritic cells are involved in apoE deficient mouse atherosclerosis. ApoE deficient mice might be a useful model for investigating functions of dendritic cells in atherogenesis.

Animals↗
PubMed1998

Mapping of vascular dendritic cells in atherosclerotic arteries suggests their involvement in local immune-inflammatory reactions.

OBJECTIVE: We previously demonstrated that vascular dendritic cells (VDCs) are present in the intima of large arteries and that their numbers are increased in atherosclerotic lesions. This study was undertaken to determine whether VDCs are involved in immune-mediated reactions in atherogenesis. METHODS: Specimens of carotid artery and aorta were obtained at operation. VDCs were identified with anti-CD1a or with S-100. Co-localisation of VDCs with different intimal cells, including T-cells and macrophages, was studied using a double immunostaining procedure. In areas where the co-localising cells were detected, the peculiarities of expression of HLA-DR, ICAM-1, VCAM-1 were examined. RESULTS: In all the atherosclerotic plaques, VDCs were seen in contact with T-cells, but these co-localising cells were irregularly distributed and were mainly found in zones of neovascularisation containing inflammatory infiltrates. In other areas, T-cell/VDC co-localisation was rarely detected but VDCs were often found in contact with macrophages. VDCs were detected also in the media beneath atherosclerotic lesions and in the adventitia, where they were mostly around vasa vasorum, especially in areas exhibiting signs of acute inflammation. In these areas VDCs expressed ICAM-1, VCAM-1 and were in contact with T-cells. In both plaques and in the adventitia, the areas with co-localising VDCs and T-cells corresponded to the areas with HLA-DR expression. CONCLUSIONS: The results suggest that VDCs are involved in T-cell activation in atherogenesis. There are two regions within the arterial wall where VDC/T-cell co-localisation mostly occurs, namely, in zones of neovascularisation containing inflammatory infiltrates located within atherosclerotic lesions, and in areas with inflammatory infiltrates around vasa vasorum in the adventitia. Possibly, some intimal VDCs migrate through the media and adventitia to adjacent lymph nodes where they present atherosclerosis associated antigens. We also speculate that VDC/macrophage contacts are essential in processing immune information in atherogenesis.

Adult↗
PubMed1998

The cell adhesion molecule E-cadherin is widely expressed in human atherosclerotic lesions.

OBJECTIVE: Various cell adhesion molecules are expressed in atherogenesis and the significance of their involvement in atherosclerotic lesion formation is well appreciated. In the present work, we examined whether the Ca(2+)-dependent cell adhesion molecule E-cadherin is also involved in atherogenesis. METHODS: Specimens of carotid artery and aorta were obtained at operation. Expression of E-cadherin was studied by an immunohistochemical method. The nature of E-cadherin-expressing cells was examined by comparative analysis of consecutive sections and by a double immunostaining procedure. An immunohistochemical approach was also applied to examine how the accumulation of oxidised low density lipoproteins (LDL) by intimal cells is associated with E-cadherin expression. RESULTS: No E-cadherin+ cells were found in normal non-atherosclerotic intima but E-cadherin+ cells were present in 96% of the atherosclerotic lesions. In atherosclerotic intima, E-cadherin was expressed by intimal cells showing varying degrees of transformation into foam cells. These E-cadherin+ cells also contained oxidised LDL in their cytoplasm. Differing numbers of CD68+ foam cells (15% to 60%) expressed E-cadherin but all the CD68+ macrophages without signs of transformation into foam cells were negative for E-cadherin. Neither smooth muscle cells nor foam cells of smooth muscle cell origin (smooth muscle alpha-actin+) were found to be positive for E-cadherin. T-cells (CD3+) and endothelial cells (von Willebrand factor+) were also negative for E-cadherin. Only a few vascular dendritic cells (S-100+) expressed E-cadherin and their expression was weak. We also found that a large proportion (40% to 85%) of E-cadherin+ cells did not stain with any cell-type specific markers. CONCLUSIONS: The finding that E-cadherin is expressed in atherosclerotic lesions expands our knowledge of cell adhesion molecules involved in atherogenesis. That E-cadherin is expressed in intimal cells transforming into foam cells suggests that lipid accumulation might be associated with the alteration and reorganisation of cell-to-cell interactions in atherogenesis. The present observations might assist in understanding the mechanisms associated with intracellular lipid accumulation.

Adult↗
PubMed1998

Detection of vascular dendritic cells accumulating calcified deposits in their cytoplasm.

The distribution of calcified microdeposits in non-atherosclerotic intima of the human aorta was studied by electron microscopy. Aortic specimens were obtained during aortic reconstruction and were embedded in Lowicryl resin. Non-stained ultrathin sections were analysed using an electron microscope equipped with an energy-dispersive X-ray microanalyser. Subsequent staining of these ultrastructural sections with lead citrate allowed us to view the tissue structures and allowed the precise location of calcified deposits in the intimal tissue to be determined. Calcium-containing microstructures were found in the extracellular matrix of the intima but, occasionally, calcium-containing microdeposits were also seen in the cytoplasm of intimal cells. Cisterns of a tubulovesicular system which is uniquely developed in cells from the dendritic cell family were detected in the calcium-containing intimal cells, which enabled these calcium-accumulating cells to be identified as a phenotype of vascular dendritic cells. These modified vascular dendritic cells might be the 'calcifying vascular cells' described previously by others.

Adult↗
PubMed1998

Immunophenotypic analysis of the aortic aneurysm wall suggests that vascular dendritic cells are involved in immune responses.

OBJECTIVE: Inflammatory infiltrates similar to those in atherosclerotic plaques are prominent in the abdominal aortic aneurysm wall. Antigen presenting vascular dendritic cells are present in both early and advanced atherosclerotic lesions but their possible participation in abdominal aortic aneurysms has not been previously examined. This study reports the presence of vascular dendritic cells in abdominal aortic aneurysms and their participation in immune responses. METHODS: Samples of the anterior wall were collected from 18 atherosclerotic infrarenal abdominal aortic aneurysms ranging in diameter from 5-8 cm. All the patients were operated upon electively and no ruptured or rapidly expanding abdominal aortic aneurysms were included. Specimens were immediately frozen or fixed in 10% buffered formalin. Vascular dendritic cells were identified with anti-CD1a or with S-100. T cells and T cell subpopulations were identified with anti-CD3, anti-CD4 and anti-CD8. B cells were studied with anti-CD20. Analyses were carried out in sets of consecutive parallel sections immunostained with these antibodies and double immunostaining included different combinations of antigens such as CD1a/CD3, S-100/CD4, S-100/CD8. RESULTS: Most inflammatory infiltrates were found in the adventitia. These infiltrates contained B cells (CD20+) and T cells (CD3+) with their CD4+ and CD3+ cell subpopulations. In the aneurysm wall, CD1a+/S-100+ cells exhibiting dendritic appearance were detected and double immunostaining demonstrated that these vascular dendritic cells contained different lymphocyte populations including CD3+, CD4+, CD8+ and CD20+ cells. In some inflammatory infiltrates, B cells (CD20+) represented the predominant cell population (60-80%). Double immunostaining demonstrated that, in these infiltrates, vascular dendritic cells contacted CD20+ cells. CONCLUSIONS: Vascular dendritic cells are involved in immune reactions in the aneurysm wall, and this process mostly occurs in the adventitia. Vascular dendritic cells contact both T cells and B cells, suggesting that these vascular dendritic cells differ from other dendritic cells, subtypes of which associate with T cells (Langerhans cells, interdigitating cells) and B cells (follicular dendritic cells).

Aorta↗
PubMed1998

Small vessel ischaemia induced by microbead embolization in the sheep hind limb.

BACKGROUND: Peripheral ischaemia may be caused by small vessel disease but there has been no satisfactory experimental model for studying this condition. We have developed a model in which microbeads are embolized to the distal vascular bed of a sheep. This model induces ischaemia proportional to the volume of microbead infusion and allows the pathophysiology and therapy of small vessel occlusion to be studied. METHODS: Gradual reduction of femoral artery blood flow by 50% and 75% in unilateral hind limbs of eight sheep was achieved by slow introduction of latex microbeads (mean size = 400 microns) into the peripheral vascular bed. The other hind limb served as a control. Measurements of blood flow, subcutaneous temperature and arterial and venous blood gases were recorded in both hind limbs after each level of flow reduction. Angiography confirmed small vessel occlusion. Muscle samples were analysed for ultrastructural changes by transmission microscopy. RESULTS: A linear correlation was found between the amount of microbeads infused and the reduction in the blood flow. Significant subcutaneous temperature and venous pO2 changes were observed in the embolized limb at both 50% and 25% flow levels compared to baseline (P < 0.05, ANOVA). Angiography demonstrated abrupt cut-off images of the small vessels. Transmission microscopy showed graded levels of muscle cell damage from ischaemia. CONCLUSIONS: Latex microbead embolization induces reproducible controlled small artery occlusion. The degree of outflow obstruction and the extent of ischaemia can be varied by delivering measured quantities of microbeads. This model should be useful for studying the pathophysiology of ischaemia and for assessing the efficacy of treatment, especially the use of pharmacological agents.

Animals↗