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Biomedical subjects

A N Orekhov

Publications and source records attributed to A N Orekhov.

At least 163 records · Page 9Linked to original sources
PubMed1987

Trapidil derivatives as potential antiatherosclerotic drugs.

Trapidil, a triazolopyrimidine, and its derivatives are coronary vasodilating drugs. Trapidil reduces the serum level of low density lipoprotein- and very low density lipoprotein-cholesterol and increases the serum level of high density lipoprotein-cholesterol in hyperlipemic patients. The present study demonstrates that trapidil and five different trapidil derivatives inhibit the proliferation of cells cultured from grossly normal intima and fatty streaks of human aorta. The inhibiting effect of trapidil derivatives is about 60%, similar to the standard substance 3-isobutyl-1-methyl-xanthine (MIX). In cells cultured from atherosclerotic plaques trapidil and trapidil derivatives reduced the content of cholesteryl esters by 36% for trapidil and between 47% and 68% for 4 of 5 trapidil derivatives, respectively. The trapidil derivative AR 12463 (5-piperidino-7-[N-(n-amyl)-N-(beta-hydroxyethyl)amino]-s-triazolo[1,5- a]pyrimidine) reduces the free cholesterol content by 29%, but the other trapidil derivatives are without effect on this parameter. Four of five derivatives decrease the content of triglycerides by 53 to 70%. The synthesis of collagen is inhibited by the trapidil derivative AR 12463 (25%). Trapidil and other derivatives have a smaller or no effect on the synthesis of collagen. These effects of trapidil derivatives point to potential antiatherosclerotic properties. The possible mechanisms are discussed.

Arteriosclerosis↗
PubMed1987

Is prostacyclin a major prostaglandin produced by endothelial cells in culture?

Prostaglandin biosynthetic activity of cultured human aortic and umbilical vein endothelial cells (passages 3-9) and of human aortic subendothelial cells (passage 0) was studied. Labelled arachidonic acid or endoperoxide H2 (final concentrations, 10 microM and 3.5 microM, respectively) were used as prostaglandin synthesis precursors. Arachidonic acid metabolites released into the incubation medium were separated by thin-layer chromatography and assayed for radioactivity. It has been demonstrated that endothelial and subendothelial cells in culture synthesize, besides prostacyclin, significant quantities of other prostaglandins, such as PGF2, PGE2, as well as thromboxane B2.

Aorta↗
PubMed1987

Comparative investigations of the reoccluded distal anastomosis, the spontaneous atherosclerotic plaque and the normal intima of the human femoral artery.

The reocclusion of the distal anastomosis in grafts of the femoral artery frequently occurs, but there is no exact information about its character. A comparative study of such reocclusions, including the nature of the spontaneous atherosclerotic plaque and of the normal intima of the human femoral artery has been performed by light-microscopic, immunomorphological and biochemical methods. Local thickening in the region of the distal anastomosis was found to resemble the atherosclerotic plaque in structure, location of several components of the extracellular matrix and in the cellular composition. These facts allow the conclusion, that progressive atherosclerosis is the cause of the reocclusion of the distal anastomosis.

Adult↗
PubMed1987

[Local prevention of thrombosis in the dog carotid artery using magnetically concentrated erythrocytes loaded with aspirin].

Thrombosis was induced in both canine carotid arteries by means of vascular wall flap inversion into their lumens. A red, completely occluding thrombus was formed inside the vessel 4 to 5 hours later. SmCo5 magnet was secured externally to one of the arteries. The constant magnetic field produced by the magnet had no influence on the clot formation. Autologous red cells loaded with ferromagnetic colloid compound and aspirin were administered intravenously through the hind paw route; total aspirin pool was 20 micrograms. Circulating magnetically-charged red cells have been earlier shown to concentrate in a canine artery in the constant magnet area. The administration of magnetically-charged red cells loaded with aspirin completely prevented arterial thrombosis in the magnet-supplied artery, having no detrimental effect on clot formation in the control artery.

Animals↗
PubMed1987

Spontaneous atherosclerotic plaque and obstruction of distal anastomosis in femoral artery. Comparative morphologic study.

The morphology of unaffected intima, atherosclerotic plaque, and postoperative obstructions of the distal anastomosis of the human femoral artery was studied by light and immunofluorescence microscopy. It was established that a focal thickening at the site of the distal anastomosis is identical with an atherosclerotic plaque in structure and localization of certain extracellular matrix components. A distinctive feature of the intimal thickening at the site of the distal anastomosis is the presence of an organized thrombus. These data suggest that obstruction of the distal anastomosis occurs due to the development of an atherosclerotic plaque complicated by an organized thrombus.

Adult↗
PubMed1987

[Effect of components of the extracellular matrix on the accumulation of lipids in human cells].

The effect of extracellular matrix components on cholesterol accumulation in different human cells was studied. Insoluble LDL-Heparin-Fibronectin-Gelatin complexes were incubated with human cells: fibroblasts, monocytes, peritoneal macrophages, cells of the aortic wall--endothelial, subendothelial intimal, medial; and total cholesterol content in these cells was determined. It has been demonstrated that components of extracellular matrix being complexed with LDL enhance total cholesterol accumulation in all cell types studied: the highest amount of cholesterol was accumulated by subendothelial intimal cells and peritoneal macrophages. It is suggested that components of extracellular matrix can play an important role in the development of lipid-laden foam cells that are accumulated in the arterial wall in atherosclerotic lesions.

Endothelium, Vascular↗
PubMed1986

Atherogenicity of blood serum from patients with coronary heart disease.

The sera from 62 of 68 patients with coronary heart disease (CHD) caused a two to five fold elevation in the intracellular cholesterol in primary cultures of subendothelial cells derived from grossly normal intima of human aorta. The sera from 33 of 42 healthy subjects did not show atherogenic properties in culture. Atherogenic potential correlated directly with the serum apolipoprotein-B-apolipoprotein A1 ratio, but not with the level of total cholesterol, high-density-lipoprotein cholesterol, apo-B, or apo-A1. The sera from patients with CHD also facilitated deposition of lipids in the medial smooth muscle cells of human aorta and mononuclear blood cells, though to a lesser degree. They had no such effect on endothelial cells of human aorta and umbilical vein, or human embryo fibroblasts.

Adult↗
PubMed1986

Adult human aortic cells in primary culture: heterogeneity in shape.

Adult human aortic cells have different shapes in situ. To determine whether populations of cultured aortic cells are also polymorphic, a technique for separation of cells from the intimal and medial layers of the human aorta by enzymatic dispersion of the vascular tissue was employed. It was established that aortic cells are polymorphic in primary culture, at least within the first 7 days after seeding. Four main morphological cell types were identified--elongated, asymmetric, polygonal, and stellate. Polygonal and stellate cells are found only in cultures of grossly normal intima. Elongated and asymmetric cells are present in practically all cultures. The ratio of elongated to asymmetric cells in cultures obtained from healthy aortas and atherosclerotic plaques is more or less the same and is approximately 3:1. In cultures of fatty streaks, the portion of asymmetric cells exceeds 50%. With immunofluorescent staining and ultra-structural analysis, cells of all four types were identified as smooth muscle. Possible reasons for the cells polymorphism in primary culture and the prospects of utilizing this culture method in the investigation of cellular aspects of atherogenesis are discussed.

Adult↗
PubMed1986

Primary culture of human aortic intima cells as a model for testing antiatherosclerotic drugs. Effects of cyclic AMP, prostaglandins, calcium antagonists, antioxidants, and lipid-lowering agents.

Smooth muscle cells isolated from atherosclerotic lesions of human aorta retain in primary culture their intrinsic in vivo characteristics: namely, enhanced proliferative activity and high lipid levels. We have tested the effect of different compounds on [3H]thymidine uptake and on the levels of phospholipids, triglycerides, cholesterol, and cholesteryl esters in cultured aortic cells. Effects, such as the inhibition of cellular proliferation and/or lowering of the intracellular lipid levels which would be regarded as antiatherosclerotic if exerted in vivo, were observed in vitro by the following compounds: dibutyryl cyclic AMP, cholera toxin, forskolin, methylisobutylxanthine, stable prostacyclin analogues, prostaglandins E2 and D2, verapamil, reserpine, alpha-tocopherol, butylated hydroxytoluene, lipostabil, and high density lipoproteins. In this paper, we discuss the possibility of using a primary culture of smooth muscle cells from an atherosclerotic human aorta for testing drugs for possible antiatherosclerotic activity.

Antioxidants↗
PubMed1986

Effect of cyclic AMP on lipid accumulation and metabolism in human atherosclerotic aortic cells.

The effects of dibutyryl cyclic AMP (db cAMP), cholera toxin, and methylisobutylxanthine on the content and metabolism of lipids in smooth muscle cells cultured from normal and atherosclerotic intima of human aorta have been studied. Db cAMP (0.1 mM) decreased the levels of triglycerides and esterified sterols 1.5-3-fold in cells cultured from fatty streaks and atherosclerotic plaques. Cholera toxin (100 micrograms/ml) and methylisobutylxanthine (0.1 mM) stimulated by 2-fold the cyclic AMP level in aortic smooth muscle cells and decreased the content of triglycerides and esterified sterols by 2-3-fold. Prolonged treatment with db cAMP and methylisobutylxanthine resulted in a fall in the intracellular phospholipids and free sterols. Using the labelled precursors, [3H]acetate and [14C]oleate, it was established that the agents increasing the intracellular cyclic AMP level inhibit the formation of sterols and fatty acids, impede the synthesis of phospholipids, triglycerides and esterified sterols, and stimulate their hydrolysis. The data demonstrate that cyclic AMP facilitates the regression of cellular lipoidosis by altering the intracellular lipid metabolism.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Low-density lipoprotein apheresis and regression of atherosclerotic plaque in vitro.

Short-term organ culture and primary cell culture of human aorta were used to study the effect of selective removal of low-density lipoproteins (LDLs) from the surrounding medium (LDL apheresis) on the lipid content of cultured tissue and cells, respectively. LDL apheresis was performed by passing the culture medium through immunosorbent containing agarose-bound goat antibodies against human LDL. LDL apheresis promoted the decrease of lipids of all classes in the cultured atherosclerotic plaque. However, only the cholesteryl ester level, but not free cholesterol, triglyceride, or phospholipid levels, was lowered in the cells cultured from the plaque. One may thus assume that LDL apheresis facilitates regression of lipoidosis by reducing the content of lipids in atherosclerotic lesions.

Aorta↗
PubMed1986

Agents that increase cellular cyclic AMP inhibit proliferative activity and decrease lipid content in cells cultured from atherosclerotic human aorta.

Cholera toxin, methylisobutylxanthine and prostacyclin (PGI2) analogues as well as dibutyryl cyclic AMP inhibit by 2-7-fold 3H-thymidine uptake into intimal cells isolated from atherosclerotic human aorta in primary culture. These agents also decrease cholesteryl ester and triglyceride levels and do not affect content of phospholipids and free cholesterol in cells cultured from atherosclerotic lesions.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Cyclic AMP and cyclic GMP content in a short-term organ culture of normal and atherosclerotic human aorta.

Cyclic AMP and cyclic GMP content was measured in intima and media of unaffected and atherosclerotic areas of human aorta in a short-term organ culture. It was demonstrated that during short-term cultivation the content of both cyclic nucleotides in tissues is constant. The cyclic AMP content in fatty streaks and atherosclerotic plaques is significantly (2 to 7-fold) lower than in unaffected intima. The cyclic GMP level in atherosclerotic lesions is 1.5 to 3-fold higher than in normal. The content of both cyclic nucleotides in the media underlying fatty streaks is the same as in the normal tissue. In the media underlying atherosclerotic plaques, the cyclic AMP level is decreased compared to the normal. The obtained data indicates serious disorders in the system of cyclic nucleotides during atherosclerosis. Possible consequences of this disfunction are discussed.

Aorta↗
PubMed1986

Monoclonal antibody reveals heterogeneity in human aortic intima: detection of a ganglioside antigen associated with a subpopulation of intimal cells.

The cells of the arterial wall are heterogeneous. To study the functions and peculiarities of various subpopulations of arterial cells the authors have generated an IgM mouse monoclonal antibody, designated 3-Lena, which interacts with human aortic cells (demonstrated by RIA and flow cytofluorometry). The cellular antigens interacting with monoclonal antibody 3-Lena are gangliosides GM3, GD3, GD1a, and GT1b. Presumably, the epitope is represented by the structure -NeuAc alpha 2----3Gal beta 1, a component of the oligosaccharide moiety of the ganglioside molecule. In addition to aortic cells, those dissociated from other large human vessels as well as cells of the myometrium and lung parenchyma interact with 3-Lena. Cells dissociated from the spleen and renal cortex exhibit a substantially weaker interaction, while liver and myocardial cells do not react. Compared with human aortic cells, aortic cells of other mammalian species stain less effectively (dog, swine) or do not stain at all (bovine, ram). Flow cytofluorometric analysis demonstrates that practically all human aorta medial cells interact with antibody 3-Lena, whereas a certain portion of cells in the intimal population do not. In the outer intimal sublayer adjoining the media, the cells reacting with monoclonal antibody 3-Lena make up the bulk of the cell population, and the inner sublayers are characterized by a prevalence of nonreactive cells. After separation of reactive and nonreactive human aortic intimal cells by a cytofluorometer-cell sorter, 3-Lena+ cells were found to have an elongated bipolar shape, whereas most 3-Lena- cells have multiple processes and variable elongated, stellate, or irregular shapes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Intimal cells and atherosclerosis. Relationship between the number of intimal cells and major manifestations of atherosclerosis in the human aorta.

The subendothelial intima of human aorta is populated by cells of various shapes. Round and ovoid cells which are lymphocyte- and monocyte-like hematogenous cells account for less than 5% of the cell population. The bulk of the intimal population (over 95%) is made up of cells that can be described as elongated, stellate, elongated with side processes, and irregularly shaped. To identify these morphologic forms, the authors have used target electron microscopy. It has been established that elongated cells devoid of side processes possess all the ultrastructural features of differentiated smooth muscle cells: a developed contractile apparatus in the form of microfilament bundles with dense bodies occupying most of the cytoplasm, basal membrane surrounding the whole of the cell, and micropinocytotic vesicles along the plasma membrane. The other morphologic forms have an ultra-structure that allows us to identify them as so-called modified smooth muscle cells. They differ from the typical smooth muscle cells in that they have fewer contractile structures and a more developed biosynthetic apparatus. Some of stellate and irregular shaped cells are utterly devoid of contractile structures. To quantitate the number of cells of different morphologic forms, the authors used alcoholic-alkaline dissociation of prefixed intima. It was established that the intimal population is multiplied at the site of an atherosclerotic lesion, the number of stellate cells being increased much more substantially, compared with other morphologic cell forms. It was found that an increase in the number of stellate cells is related to such sequelae of atherosclerosis in aorta as intimal thickening, deposition of lipids, and an increased amount of collagen. There was a high positive correlation between the alteration in the stellate cell number occurring in the intima and the above-mentioned parameters (correlation coefficients were 0.732, 0.800 and 0.953, respectively). The correlations between these indexes and the total number of intimal cells or the number of cells belonging to each of the other morphologic forms were not so high. A multivariate analysis gave similar results. Thus, it may be suggested that stellate cells are the principal cell type involved in the disease. This report discusses the origin of stellate and other intimal cells and their role in atherogenesis.

Adult↗
PubMed1985

Determination of total intracellular lipid content by flow cytofluorometry.

It was demonstrated that perylenoyl-labeled triglyceride, rac-1,2-dioleoyl-3-[9(3-perylenoyl)nonanoyl]glycerol (PLTG), specifically stains the intracellular lipids in formalin-fixed and non-fixed cells in situ and in suspension. The fluorescence of labeled cells was registered on a FACS-II cytofluorometer. It was found that the mean intensity of fluorescence in PLTG-labeled cells of various types, both fixed and non-fixed, correlates with their total lipid content. There was no correlation, however, between the mean intensity of fluorescence and intracellular levels of lipids belonging to different classes: phospholipids, triglycerides, cholesterol or cholesteryl esters.

Animals↗