Biomedical subjects

A N Orekhov

Publications and source records attributed to A N Orekhov.

At least 109 records · Page 6Linked to original sources

PubMed1991

Use of cultured atherosclerotic cells for investigation of antiatherosclerotic effects of anipamil and other calcium antagonists.

Calcium antagonists have been shown to exhibit an antiatherosclerotic action in primary cultures of human aortic atherosclerotic cells by causing a reduction in intracellular lipid content, proliferative activity and synthesis of the extracellular matrix. Verapamil and nifedipine exhibited the highest efficacy in this respect. The new calcium antagonist, anipamil (racemate and enantiomers), has been tested in cell cultures. At 10(-6) M and higher concentrations, anipamil and its enantiomers produced considerable decrease in intracellular content of cholesteryl esters, triglycerides and free cholesterol, suppressed cell proliferation and inhibited synthesis of the extracellular matrix. The efficacy of anipamil (enantiomers and racemate) was similar to that of verapamil and greater than that of nifedipine. Plasma obtained from patients after administration of 80 mg verapamil or 20 mg nifedipine significantly lowered the cholesterol content of cultured cells. Blood plasma of most atherosclerotic patients possesses atherogenic properties, i.e., it is able to increase the cholesterol content in cultured cells. Plasma atherogenicity seen in cultures decreased considerably or even disappeared after both nifedipine and verapamil administration. After 28 days of nifedipine therapy, plasma atherogenicity was lower compared with the initial value at the beginning of the treatment. These observations suggest that control of plasma atherogenicity after drug administration may provide an additional tool for optimisation of direct antiatherogenic and antiatherosclerotic therapy.

Aorta↗

PubMed1991

Lipoprotein immune complexes as markers of atherosclerosis.

Recently we have demonstrated that cholesterol level in LDL-containing circulating immune complexes (CIC cholesterol) correlates with the presence of coronary atherosclerosis. In the present study we attempted to clarify whether CIC cholesterol level correlates with the severity of coronary atherosclerosis. The second task was to reveal the diagnostic value of CIC cholesterol in comparison with other lipid and lipoprotein parameters used as markers of dislipidaemia associated with atherosclerosis. The subjects were 107 patients with angiographically-documented coronary atherosclerosis and 66 patients with documented extracoronary atherosclerosis. Only CIC cholesterol and the apo B/apo A-1 ratio contributed strongly to the discrimination between patients with coronary atherosclerosis and those without stenoses. On the other hand, total cholesterol, triglycerides, HDL cholesterol, apo B, Lp[a] and apo A1 did not correlate with the presence and severity of coronary atherosclerosis. Subjects with stenosis of extracoronary arteries had significantly higher CIC levels than healthy donors. Sensitivity, specificity and accuracy of coronary atherosclerosis diagnosis were assessed for each parameter examined. It was revealed that CIC cholesterol is the most reliable marker of coronary atherosclerosis as compared to other chemical parameters. In addition, the CIC cholesterol level diagnoses extracoronary atherosclerosis with high accuracy.

Adult↗

PubMed1991

[The cellular polymorphism of the myointimal thickening in the rabbit aorta].

Partly endothelialized myointimal thickening formed in rabbit aorta after balloon catheter injury. It was populated by cells of different shape. There were spindle-shaped cells. Y-shaped cells, cells of irregular shape with processes and stellate-shaped cells. As a rule stellate cells situated just near the endothelium. It is supposed, that the endothelium can influence the shape of myointimal cells.

Animals↗

PubMed1991

[Changes in the 3-dimensional organization of the cellular system of the human aortic intima in atherosclerosis].

Three-dimensional organization of the subendothelial aortal intima was studied by means of light microscopy of serial membranous preparations and scanning electron microscopy. Three-dimensional network composed of cells of varying shape is found in normal intima. Lipid inclusion in the lipid streak are found mainly in the stellate and roundish cells. Intercellular links are destroyed in the superficial layers of the lipid streak with extracellular lipid droplets being found in the region of the contact rupture. The cells are practically deprived of contacts in the marginal zone and central part of the atherosclerotic plaque cover where giant stellate cells integrated into the rough fibrillar connective tissue matrix are frequently found.

Adult↗

PubMed1991

[Atherogenic effect of beta-blocker propranolol revealed in the rabbit denudated aorta].

The influence of beta-blocker propranolol onto atherogenic properties of blood serum and to formation of myointimal thickening in rabbit aorta, which was caused by denudation, were investigated. The preparation was introduced per os in the dose 6 mg/kg. Culture of mouse peritoneal macrophages was used to estimate the atherogenic properties of the serum. Serum of propranolol-treated rabbits induced accumulation of cholesterol in cultivated cells. Propranolol also induced an increase of the thickness of aortic intima, lipid accumulation and increasing of cell's number in myointimal thickening. Thus, atherogenic effect of beta-blocker propranolol was found both in vitro and in vivo.

Administration, Oral↗

PubMed1991

Three-dimensional cytoarchitecture of normal and atherosclerotic intima of human aorta.

The three-dimensional cytoarchitecture of normal and atherosclerotic intima of human aorta was studied by light microscopy of consecutive en face preparations (Hautchen preparations) and by scanning electron microscopy. In unaffected intima, a three-dimensional network consisting of cells of variable shape and probably origin was demonstrated. Cellular shape changed from predominantly stellate in the luminal regions of the elastic-hyperplastic layer to elongated spindlelike cells in the musculoelastic layer of the intima. In the surface layers of the fatty streak, cellular contacts were severed, and lipid droplets were often seen between cellular processes. Along with stellate and elongated cells, the fatty streak also had a number of round monocytelike cells. Lipid inclusions were usually detected in stellate and ovoid cells. The integrity of the cellular network was preserved at the marginal zone of the atherosclerotic plaque, while at the slopes and in the central part of the plaque, cells practically lost all contact with each other. Giant stellate cells embedded in crude fibrillar connective tissue matrix were often found there. Disintegration of the cellular network during atherosclerosis is suggested to play an important role in the development of various lesions.

Adult↗

PubMed1991

[Relations between the levels of lipoprotein-containing immune complexes and lipids in the blood of patients with ischemic heart disease].

The sera from most patients with coronary heart disease concurrent with angiographically documented coronary atherosclerosis were found to contain apolipoprotein B (Apo B), neither apolipoprotein E (Apo E) nor apolipoprotein AI (Apo AI) in the circulating immune complexes precipitated by polyethylene glycol-6000 (PEG). Low density lipoproteins are the major components of cholesterol-containing immune complexes precipitated by PEG. A correlation was established between the serum levels of total cholesterol (r = 0,74; p less than 0.01), and low density lipoprotein (LDL) cholesterol (r = 0.77; p less than 0.01) in patients with coronary heart disease and cholesterol in LDL-containing No relationship was found in healthy individuals. The in vitro increase in LDL levels in most patients with coronary heart disease concurrent with coronary atherosclerosis was not followed by an elevation in LDL-containing immune complexes.

Antigen-Antibody Complex↗

PubMed1991

[Circulating immune complex cholesterol as a biochemical marker of coronary atherosclerosis].

The study was undertaken to examine 134 patients who were divided into 2 groups: 1) those with angiographically documented coronary atherosclerosis and 2) those with unaltered coronary arteries. The levels of immune complex cholesterol and the parameters of serum lipid spectrum were investigated in all the patients. The level of immune complex cholesterol and the apo B/apo AI ratio were the most informative indices in the characterization of coronary atherosclerosis. Immune complex cholesterol may be used as a marker of coronary atherosclerosis, the diagnostic accuracy is 78% with this method.

Adult↗

PubMed1991

[Structure of the neointima after balloon catheter injury of the rabbit aorta in the context of hypercholesterolemia: analysis of endothelial influence on lipid accumulation].

Balloon catheter de-endothelialization of abdominal aorta of cholesterol-fed rabbits was performed. As a result, partly endothelialized neointima was formed, consisting of smooth muscle cells and macrophages. Neutral lipids stored more intensely in non-endothelialized part of neointima. Preferential intracellular lipid accumulation in this area was observed while predominantly extracellular lipid accumulation was found in endothelium-covered part of neointima. It is supposed that endothelium inhibits intracellular lipid accumulation and at the same time stimulates an extracellular one, but as a whole it reduces the density of lipid inclusions in neointima.

Animals↗

PubMed1990

In vitro models of anti-atherosclerotic effects of cardiovascular drugs.

In studies performed on cells isolated from the subendothelial intimal layer of both normal and atherosclerotic human aortas, cells from atherosclerotic lesions retained atherosclerotic properties while in primary culture, including enhanced proliferative activity and high lipid level. The content and composition of lipids in cultured cells remained unchanged for the first 10 to 12 days in culture and corresponded to the respective indices in freshly isolated cells. When added to an atherosclerotic cell culture, the calcium antagonist verapamil reduced the total intracellular cholesterol level by threefold and inhibited proliferation and collagen synthesis by cultured cells within 48 hours. Of the 12 calcium antagonists tested, verapamil and nifedipine demonstrated the greatest antiatherosclerotic activity. In contrast, nitrates had no effect on atherosclerotic parameters, while beta blockers increased atherosclerotic manifestations of cultured cells. In studies in which plasma was added to cell cultures, 2 to 4 hours after patients received oral nifedipine or verapamil, their plasma prompted antiatherosclerotic responses from cell cultures by reduced intracellular cholesterol and inhibited atherosclerotic cell proliferation. Plasma of patients who received oral propranolol, however, demonstrated atherogenic characteristics. The atherogenic properties of propranolol were inhibited by nitroglycerin and nifedipine. Use of the atherosclerotic cell model allows the examination of the atherogenic and antiatherogenic properties of various drugs, thus possibly optimizing antiatherosclerotic therapy.

Arteriosclerosis↗

PubMed1990

Isolation of atherogenic modified (desialylated) low density lipoprotein from blood of atherosclerotic patients: separation from native lipoprotein by affinity chromatography.

A part of low density lipoproteins (LDL) isolated from the blood of healthy subjects and patients with coronary atherosclerosis bind to a Sepharose-linked Ricinus communis agglutinin, a lectin that interacts specifically with galactose residues. Bound LDL can be replaced by galactose, but not other saccharide constituents of the LDL molecule (mannose, glucose, N-acetylglucosamine, sialic acid). Bound LDL subfraction has a 2-3-fold lower content of sialic acid as compared with unbound LDL. The blood content of desialylated LDL in atherosclerotic patients was about 3-fold higher (1.5- to 6-fold) than in healthy subjects. Desialylated LDL induced a 2- to 4-fold more intensive accumulation of total cholesterol in cultured human aortic intimal cells. Unbound LDL had no effect on intracellular deposition of lipids. It is suggested that the subfraction of desialylated LDL may be responsible for the atherogenicity of LDL isolated from blood of atherosclerotic patients.

Adult↗

PubMed1990

Local prevention of thrombosis in animal arteries by means of magnetic targeting of aspirin-loaded red cells.

Thrombosis was induced in 18 dog and 16 rabbit arteries by surgically inverting a vascular wall flap into its lumen. A completely occluding red thrombus was formed inside the vessel 4 to 5 hours later in 80% of cases. 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 and completely aborted arteriothrombosis on magnet-supplied side with no deterioratory effect on clot formation in the control artery.

Animals↗

PubMed1990

Low density lipoprotein-containing circulating immune complexes and coronary atherosclerosis.

Blood serum of most patients with coronary heart disease (CHD) caused a 2- to 5-fold increase in the lipid content of smooth muscle cells cultured from unaffected human aortic intima, i.e., possessed an atherogenic potential manifested in culture. Treatment of the CHD patients' serum with 2.5% polyethylene glycol 6000 removed the circulating immune complexes. The serum subjected to this treatment lost its atherogenic properties, i.e., failed to increase the content of lipids in cultured cells. Incubation of smooth muscle cells derived from human aortic intima with circulating immune complexes isolated from an atherogenic patient's serum caused a 1.5- to 3-fold rise in the intracellular cholesterol. Circulating immune complexes contained apolipoprotein B (apo B), but not apolipoproteins A1 and E. The apo B content strongly correlated with the total cholesterol content. The cholesterol/apo B ratio of the complexes was characteristic of low density lipoproteins (LDL), but not of very low density lipoproteins or intermediate density lipoproteins. The composition of the main lipid classes in these complexes was similar to that in LDL. Blood sera of most (90%) CHD patients was characterized by a high cholesterol and apolipoprotein B content in circulating immune complexes. The ability of these sera to induce lipid accumulation in cultured cells directly correlated with the cholesterol and apolipoprotein B level of circulating immune complexes (r = 0.91). These findings suggest that the atherogenic potential of CHD patients' blood serum is due to LDL-containing immune complexes.

Adult↗

PubMed1990

Correlation between cholesterol content in circulating immune complexes and atherogenic properties of CHD patients' serum manifested in cell culture.

Blood serum of most patients with coronary heart disease (CHD) caused a 2-5-fold increase in the total cholesterol content of smooth muscle cells cultured from unaffected human aortic intima, i.e. possessed an atherogenic potential manifested in culture. Removal of immunoglobulins G and M from an atherogenic serum brought about a fall in its atherogenic potential. The serum deficient in immunoglobulins A retained its ability to induce the cholesterol accumulation in cells. Treatment of the CHD patients' serum with 2.5% polyethylene glycol 6000 removed the circulating immune complexes. The serum subjected to this treatment lost its atherogenicity, i.e. failed to increase the cholesterol content in cultured cells. Incubation of smooth muscle cells derived from human aortic intima with circulating immune complexes isolated from an atherogenic patients' serum caused a 1.5-3-fold rise in the intracellular cholesterol. Blood sera of most (89%) CHD patients was characterized by a high cholesterol content in circulating immune complexes. More than 75% of healthy subjects and patients without stenosis of coronary arteries had low level of cholesterol in immune complexes. Blood sera atherogenicity manifested in culture directly correlated with the cholesterol level of circulating immune complexes (r = 0.90). These findings suggest that the atherogenicity of CHD patients blood serum is due to cholesterol-containing immune complexes.

Adult↗

PubMed1990

Triggerlike stimulation of cholesterol accumulation and DNA and extracellular matrix synthesis induced by atherogenic serum or low density lipoprotein in cultured cells.

A 72-hour incubation of cultured cells with blood sera or plasma of patients suffering from coronary heart disease (CHD) with angiographically assessed coronary atherosclerosis caused a threefold to fourfold elevation of intracellular cholesterol. An elevated cholesterol level in the cells precultured with patients' sera was retained several days after the removal of the examined serum from culture. The accumulation of intracellular cholesterol was accompanied by enhanced synthesis of DNA, total protein, collagen, sulfated glycosaminoglycans, and hyaluronic acid. Enhanced DNA and total protein synthesis was retained for at least 9 days after the serum had been removed from culture. The obtained results suggest that the sera of CHD patients possess an atherogenic potential that manifests itself at the arterial cell level in the stable stimulation of atherosclerotic cellular processes: proliferation, lipidosis, and fibrosis. The examined sera of healthy donors were devoid of such an atherogenic potential. The low density lipoprotein (LDL) fraction (density, 1.030-1.050 g/cm3) obtained from an atherogenic serum had the same atherogenic potential as a whole serum. Atherosclerotic alterations in cultured intimal cells caused by atherogenic LDL were retained for at least 3 days after the removal of the lipoprotein from culture. Preincubation of intimal cells with LDL obtained from healthy donors had no effect on the intracellular cholesterol level or the synthesis of DNA and extracellular matrix. One may assume that the atherogenic potential of CHD patients' sera is related to the presence of LDLs that are qualitatively different from the LDL of healthy subjects.

Blood Physiological Phenomena↗

PubMed1990

Antiatherosclerotic effects of calcium antagonists. Study in human aortic cell culture.

To investigate the effects of calcium antagonists on atherosclerotic cellular indices, [3H]thymidine incorporation and intracellular cholesterol content, primary culture of cells isolated from subendothelial intima of human atherosclerotic aorta was used. Among tested drugs were: verapamil, nifedipine, diltiazem, papaverin, nicardipine, D-600, cinnarizine, PN 200 110 and PY 108 068. Verapamil proved to be the most effective. It significantly reduced the total intracellular cholesterol and sharply decreased the incorporation of [3H]thymidine. With respective efficacy verapamil was followed by nifedipine and PY 108 068. Neither beta-blocker (metoprolol) nor nitrate (nitroglycerin) modified antiatherosclerotic effects of calcium antagonist (nifedipine). Calcium agonist Bay K 8644 which facilitates the penetration of calcium into cells caused the accumulation of intracellular cholesterol and stimulated cell proliferation. Simultaneous addition of nifedipine and Bay 8644 led to the inhibition of the agonist's atherogenic effect. Thus, facilitation of calcium influx into cells causes atherosclerotic alterations in the arterial cells; atherogenic calcium effects are inhibited by calcium channel blockers. Furthermore, based on the results of application of blood plasma from patients treated with calcium antagonists or beta-blocker to primary cultures of atherosclerotic cells, it can be assumed that calcium antagonists affect an anti-atherosclerotic and beta-blockers an atherogenic action.

Adrenergic beta-Antagonists↗

PubMed1990

[Isolation of desialylated low density lipoproteins from the blood of patients with ischemic heart disease by affinity chromatography].

The attempt was performed to isolate desialylated low density lipoproteins (LDL) from the blood of healthy subjects and patients with coronary heart disease by affinity chromatography with immobilized agglutinin of Ricinus communis, a lectin that interacts specifically with galactose residues. A part of LDL was bound to sorbent and could be replaced by galactose but not other saccharide constituents of the LDL molecule. Bound LDL subfraction had a 2-3-fold lower content of desialylated LDL in CAD patients was about 3-fold higher than in healthy subjects. Desialylated LDL induced a 2- to 4-fold increase of total cholesterol content in cultured human aortic intimal cells, whereas unbound LDL had no effect on intracellular cholesterol level. It is assumed that the subfraction of desialylated LDL may be responsible for the atherogenic properties of LDL in CAD patients.

Adult↗

PubMed1990

[The use of freeze fracturing in combination with light, scanning and transmission electron microscopy for studying the structure of the normal and atherosclerotically altered human aortic intima].

Three-dimensional network of smooth muscle cells (SMC) with processes was found in the subendothelial intima of human aorta. The cells were connected with each other through gap junctions. In the direction from the media to the endothelium the number of plasma membrane caveolae increased, their distribution becoming more random. In the fatty streak, the integrity of cellular network was seen destroyed. In the extracellular matrix multilamellar ball-like structures containing large intramembranous particles appeared. In the fibrous plaque, SMCs are completely isolated by connective tissue fibres.

Aorta, Thoracic↗