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Biomedical subjects

A N Orekhov

Publications and source records attributed to A N Orekhov.

At least 91 records · Page 5Linked to original sources
PubMed1992

[Atherogenic properties of phenothiazine drugs manifesting in cultured cells of the human aortic intima].

The effects of phenothiazine drugs on the levels of cholesterol in smooth cells of the human aortic intima. Two antiarrhythmics (ethacizin and ethmozine) and two neuroleptics (trifluoperazine and chlorpromazine) were evaluated. The three agents ethacizin, trifluoperazine, and chlorpromazine given in concentrations of 10(-7) to 10(-5) M were ascertained to cause intracellular cholesterol accumulation, whereas ethmozine produced no effects on the intracellular levels of cholesterol. Ethacizin failed to cause cholesterol accumulation when the cells were incubated with ethacizin in the culture medium supplemented with lipid-deficient serum. Ethacizin in a concentration o 10(-5) M was shown to inhibit the synthesis of cholesterol esters and had no action on the intracellular synthesis of steroids.

Anti-Arrhythmia Agents↗
PubMed1992

[Elimination of the atherogenic effect of beta blocker propranolol by papaverine].

Recently, the ability of beta-blockers to stimulate proliferative activity and induce lipid accumulation in cultured human aortic intimal cells has been demonstrated. Moreover, the addition of calcium antagonists completely blocked the increase in proliferative activity and abolished cholesterol accumulation caused by propranolol. In this study blood serum of rabbits treated with 20 mg of propranolol induced 2-fold cholesterol accumulation in mouse peritoneal macrophages. Papaverin did not influence this effect. In case of simultaneous administration of propranolol and papaverin rabbit serum did not exhibit the ability to accumulate intracellular lipids. Propranolol substantially stimulated the formation of myointimal thickening and neutral lipid accumulation in denuded rabbit aorta. Papaverin completely blocked the propranolol-produced atherogenic changes. The data suggest that in vitro and in vivo atherogenic effects of beta-blockers may be prevented by papaverin.

Animals↗
PubMed1992

Multiple-modified desialylated low density lipoproteins that cause intracellular lipid accumulation. Isolation, fractionation and characterization.

BACKGROUND: The basic differences between sialylated (sialic acid rich) and desialylated (sialic acid poor) human low density lipoproteins (LDL) are not fully defined. It is not known whether there are any differences in the LDL composition of coronary atherosclerosis patients and healthy individuals. EXPERIMENTAL DESIGN: Sialylated (45 to 94% of total LDL) and desialylated (6 to 55%) LDL were separated by affinity chromatography on Ricinus communis agglutinin-agarose, and their chemical composition and physical properties were examined. RESULTS: Sialic acid contents in sialylated LDL fractions of healthy subjects and patients were the same and 1.5 to 3-fold higher than in desialylated LDL. Desialylated LDL had smaller sizes and greater electrophoretic mobility than sialylated ones. Desialylated, but not sialylated LDL, induced 1.5- to 4-fold accumulation of neutral lipids in human aortic smooth muscle cells and human blood monocytes. Subfractions of desialylated LDL containing lower amount of sialic acid revealed higher ability to accumulate lipids in cultured cells. Desialylated LDL contained lower amounts of cholesteryl esters, free cholesterol and triglycerides as compared with sialylated LDL. On the other hand, concentration of di-, monoglycerides and free fatty acids in desialylated LDL was 2 to 3-fold higher than in sialylated lipoproteins. Desialylated LDL fraction was characterized by lower levels of phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, but higher content of lysophosphatidylcholine. Freshly isolated sialylated and desialylated LDL contained equal amounts of thiobarbituric acid reactive substances, but oxidation of desialylated LDL was more pronounced in presence of Cu(2+)-ions. Desialylated LDL had higher level of oxysterols and lower amounts of vitamin A and E. Content of free amino groups of lysine in desialylated LDL of patients was 2-fold lower than in sialylated LDL. This difference was partially due to masking of amino groups caused by conformational change in the tertiary structure of apolipoprotein, partially to chemical modification of amino groups. When subfractionated by density gradient ultracentrifugation, desialylated LDL was represented by higher density particles than sialylated LDL. Sialic acid content in desialylated LDL subfractions decreased with rise of lipoprotein density. Higher density desialylated LDL and in less extent sialylated LDL contained smaller amounts of free and esterified cholesterol and phospholipids. Only the densest subfractions of desialylated LDL from healthy subjects caused intracellular lipid accumulation. Ability of patients' desialylated LDL to accumulate cholesterol in cells increased with particle density. CONCLUSIONS: Extensive biochemical and biophysical analysis performed in this study shows that desialylated LDL differ from these sialylated LDL in many respects. The LDL of coronary atherosclerosis patients differ from those in healthy individuals in several parameters.

Adult↗
PubMed1992

Characterization of desialylated low-density lipoproteins which cause intracellular lipid accumulation.

The properties of sialylated (sialic acid rich) and desialylated (sialic acid poor) fractions of low-density lipoproteins (LDL) isolated from blood plasma of healthy subjects and coronary atherosclerosis patients have been investigated. Sialylated (60-90% of total LDL) and desialylated (10-40%) LDL were separated by affinity chromatography on Ricinus communis agglutinin-agarose. Sialic acid contents in sialylated LDL fractions of healthy subjects and patients were found to be the same, and 1.5 to 3-fold higher than in desialylated LDL. Desialylated LDL had smaller sizes and greater electrophoretic mobility than sialylated, ones. Desialylated, but not sialylated, LDL induced 1.5 to 4-fold accumulation of neutral lipids in human aortic smooth-muscle cells. Desialylated LDL contained lower amounts of cholesteryl esters, free cholesterol and triglycerides as compared to sialylated LDL. On the other hand, the concentrations of di-, monoglycerides and free fatty acids in desialylated LDL were 2 to 3-fold higher than in sialylated lipoproteins. The desialylated LDL fraction was characterized by lower levels of phosphatidylcholine, sphingomyelin and phosphatidylethanolamine, but a higher content of lysophosphatidylcholine. Levels of thiobarbituric acid-reactive substances in freshly isolated desialylated and sialylated LDL were the same. Desialylated LDL had a higher level of oxysterols and lower amounts of vitamins A and E. The content of free amino groups of lysine in desialylated LDL of patients was 2-fold lower than in sialylated LDL. The results of this study demonstrate that multiple physico-chemical parameters of desialylated LDL differ from those of sialylated LDL.

Adult↗
PubMed1992

Sialic acid content of human low density lipoproteins affects their interaction with cell receptors and intracellular lipid accumulation.

Low density lipoproteins (LDL) isolated from the plasma of patients with angiographically demonstrable coronary heart disease (CHD) induced accumulation of triglycerides, free cholesterol, and cholesteryl esters in cultured macrophages, smooth muscle cells, and endothelial cells derived from uninvolved intima of human aorta, but not in skin fibroblasts or hepatoma cells. The sialic acid content of LDL from CHD patients was 40-75% lower than that from healthy donors. There was a negative correlation between LDL sialic acid content and the LDL-induced accumulation of total intracellular cholesterol. Neuraminidase treatment of LDL from normal healthy donors produced sialic acid-depleted LDL (Ds-LDL) which was able to stimulate intracellular lipid accumulation. Neuraminidase treatment of LDL from CHD patients further increased its capacity to induce intracellular lipid accumulation. Sialic acid-poor LDL isolated by affinity chromatography of LDL from CHD patients induced a 2- to 4-fold increase of free and esterified cholesterol in human intimal smooth muscle cells. Binding, uptake, and degradation of 125I-labeled Ds-LDL by macrophages and endothelial cells were 1.5- to 2-fold higher than for native LDL. Binding and uptake of Ds-LDL was inhibited 64-93% by the addition of 20-fold excess acetylated LDL (Ac-LDL); in the inverse experiment, the level of inhibition was 35-54%. These data indicate that a sialic acid-poor form of LDL isolated from CHD patients can interact with both native and scavenger LDL receptors. A sialic acid-poor form of LDL may be a naturally occurring ligand that interacts with the scavenger receptor(s) on macrophages and endothelial cells.

Adult↗
PubMed1992

[Comparison between seasonal changes in lipid indicators in patients with post-infarction cardiosclerosis and arterial hypertension in Ashkhabad and Moscow].

The study was undertaken to examine 190 males, aged 30-60 years who were divided into 4 groups: (1) patients with essential hypertension; (2) those with postinfarction cardiosclerosis; (3) those with postinfarction cardiosclerosis and essential hypertension; (4) healthy individuals. The levels of apolipoproteins B and A1 and circulating immune complex cholesterol were examined in the cold (winter) and hot (summer) seasons in the areas of arid (Ashkhabad) and temperate (Moscow) climate. The major apo-proteins were determined by enzyme uncompetitive immunoassay. Cholesterol levels in the immune complexes were measured by the method developed at the Institute of Experimental Cardiology, All-Union Cardiology Research Center, USSR Academy of Medical Sciences. The Moscow examinees were found to have more profound changes in the lipid spectrum than the Ashkhabad ones. In both climatic zones, the level of the major apo-proteins and their ratio were unaffected by seasonal variations.

Adult↗
PubMed1991

Lipids in cells of atherosclerotic and uninvolved human aorta. III. Lipid distribution in intimal sublayers.

The distribution, content, and composition of tissue and cellular lipids in intimal layers of unaffected and atherosclerotic human aorta were studied. Aortic tissue was divided into medial and intimal layers; the intimal layer was further separated into elastic-hyperplastic and musculo-elastic sublayers. Cells were isolated from both intimal layers by enzyme digestion. The lipids extracted from whole tissue and cells were separated by TLC and analyzed by scanning densitometry. The highest content of phospholipids (PhL), triglycerides (TG), cholesterol (C), and cholesteryl esters (CE) was detected in the elastic-hyperplastic layer of atherosclerotic plaque. However, taking into account that the elastic-hyperplastic layer of intima in lesioned areas was thickened, the lipid content per volume unit of both sublayers in fatty streaks and in plaques was equal. In the media underlying an atherosclerotic plaque, an increase in CE rather than in other lipid classes occurred. In the intima, an overall increase in PhL, TG, C, and CE content was found to display a constant ratio between these lipid classes, similar to that of low density lipoproteins (LDL). Cells isolated from atherosclerotic lesions had a higher lipid content than cells from areas of unaffected intima. However, the increase in the content of different lipid classes was not proportional, compared with tissue lipids. The content of PhL was the same, while an increase in TG, C, and CE was observed. The major contribution to excess cellular lipid accumulation in cells from atherosclerotic lesions was made by CE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Synergetic effect of desialylated and glycated low density lipoproteins on cholesterol accumulation in cultured smooth muscle intimal cells.

We have studied the combined effect of non-enzymatically glycosylated and desialylated low density lipoproteins (LDL) on the cholesterol content of cells cultured from unaffected human aortic intima. Native LDL did not alter the intracellular cholesterol level while glycated LDL taken in the concentration percent, respectively. The effect of the same concentrations of glycated LDL treated with neuraminidase (desialylated-glycated LDL) was twice as powerful. Desialylated LDL in the concentration of 50 and 100 micrograms/ml raised the cholesterol level by 1.4- and 2.1-fold, respectively. Simultaneous incubation of cells with glycated (50 micrograms/ml) and desialylated (50 micrograms/ml) LDL brought about a 3.4-fold increase in intracellular cholesterol. The obtained data suggest that intensive development of atherosclerosis in diabetes mellitus may be partially explained by synergetic effects of desialylated and glycated lipoproteins as well as LDL with both types of modification.

Arteriosclerosis↗
PubMed1991

Desialylated low density lipoprotein--naturally occurring modified lipoprotein with atherogenic potency.

We have recently established that low density lipoprotein (LDL) of most patients with coronary atherosclerosis differs from the LDL of most healthy subjects by its ability to cause primary atherosclerotic changes, i.e. the accumulation of intracellular cholesterol in the cells of smooth muscle origin cultured from unaffected intima of human aorta. Patients' LDL has a 2.5-5-fold lower content of sialic acid as compared with the LDL of healthy subjects. On the other hand, desialylation of native LDL with neuraminidase makes it capable of causing accumulation of intracellular cholesterol similar to patients' LDL. In the present study we showed that LDL of patients and healthy donors did not differ in the content and composition of protein and lipids. Thus, the difference in the content of sialic acid is the only difference observed between atherogenic LDL of patients and nonatherogenic LDL of healthy donors. A low content of sialic acid is characteristic of both protein and lipid moiety of LDL particle. Sialic acid content was determined in individual LDL preparations obtained from patients and healthy donors. The sialic acid of LDL preparations of 25 out of 27 patients was below 18 micrograms/mg protein. LDL from 2 patients with higher sialic acid content proved to be normal. The ability of patients' LDL and LDL desialylated with neuraminidase in vitro to cause the accumulation of intracellular lipids correlated with the degree of lipoprotein desialylation. Apparently, the ability of patients' LDL to stimulate the cellular lipid accumulation may be explained by a deficiency of sialic acid in the lipoprotein particle.

Adult↗
PubMed1991

Quantitative estimation of lipid-laden cells in atherosclerotic lesions of the human aorta.

The intima of the adult human aorta consists of three sublayers: a muscular layer lying next to the media, a median hyperplastic layer and an innermost connective tissue layer, adjoining the lumen. The cells inhabiting these sublayers were isolated by the method of alcoholic-alkaline dissociation from grossly normal areas, fatty streaks and atherosclerotic plaques. The populations obtained contained cells with different numbers of cytoplasmic inclusions and a number without any. In unaffected intima and in fatty streaks, the cells with lipid inclusions were found predominantly in the outermost intimal layer including the connective tissue and in part of the median hyperplastic layer. In the superficial layer of unaffected intima and the fatty streak, these cells accounted for 15 and 25% of the total cell population, respectively. In the plaque, most cells with lipid inclusions were localized in the median hyperplastic layer of the intima (10%). The muscular layer was characterized by the lowest content of cells with lipid inclusions both in the unaffected intima and atherosclerotic lesions (from 0.75% in unaffected intima to 5% plaques). Among the intimal smooth muscle cells of various shapes, the cells with lipid inclusions were most often found in the stellate cell subpopulation (5-35%). A possible role of stellate cells in atherogenesis is discussed.

Aorta↗
PubMed1991

[Combined effects of desialylated and glycosylated low density lipoproteins on lipid content of human aortic intima cells in vitro].

We have studied a combined effect of glycosylated low density lipoproteins (LDL) on the cholesterol content of cells cultured from unaffected human aortic intima. Native LDL did not alter the intracellular cholesterol level while glycosylated LDL taken in the concentration of 50 and 100 mg/ml increased the cell cholesterol content by 30 and 70 percent, respectively. The effect of the same concentrations of glycosylated LDL treated with neuraminidase (desialylated-glycosylated LDL) was twice as powerful. Desialylated LDL in the concentration of 50 and 100 mg/ml raised the cholesterol level by 1.4- and 2.1-fold, respectively. Simultaneous incubation of cells with glycosylated (50 mg/ml) and desialylated (50 mg/ml) LDL brought about a 3.4-fold increase in intracellular cholesterol. The obtained data suggest that intensive development of atherosclerosis in diabetes mellitus may be partially explained by synergic effects of desialylated and glycosylated lipoproteins as well as LDL with both types of modification.

Aorta↗
PubMed1991

[Atherogenic properties of sera and low-density lipoproteins in patients with diabetes mellitus].

The effects of sera and low density lipoproteins (LDL) on cholesterol levels were evaluated in cultured aortic intimal cells from patients with Types 1 and 2 diabetes mellitus. About 80% Type 1 diabetic patients' sera and 90% of Type 2 diabetic patients' sera caused a 1.5-4-fold increase in intracellular cholesterol levels. LDL isolated from atherogenic sera induced intracellular cholesterol accumulation. There was a close correlation between the atherogenic effect of the sera and LDL. The atherogenic properties of the sera and LDL from patients with diabetes mellitus were unassociated with the examinees' age. There was a relationship between the atherogenic serum effect and the compensation of carbohydrate metabolism in male patients with Type 1 diabetes mellitus. The atherogenic effect of the sera and LDL failed to increase in patients with Types 1 and 2 diabetes mellitus concurrent with coronary heart disease. The property of the sera to accumulate intracellular cholesterol is likely to be typical of diabetes mellitus and mainly due to disturbed LDL metabolism.

Adult↗
PubMed1991

[Seasonal variations of the lipid spectrum in patients with post-infarction cardiosclerosis and arterial hypertension].

The lipid spectrum was examined in 77 Moscow male residents aged 30-60 years in winter and in summer. The examinees were divided into 4 groups: (1) healthy subjects; (2) patients with arterial hypertension; (3) those with post-infarction cardiosclerosis; (4) those with the two abnormalities. The levels of total cholesterol, triglycerides, high density lipoprotein cholesterol, low and very low density lipoprotein cholesterol, and circulating immune complex cholesterol were measured. All the groups were demonstrated to have lower cholesterol and low density lipoprotein levels in summer than in winter, which should be taken into account in the diagnosis and treatment of atherosclerosis-associated diseases.

Adult↗
PubMed1991

[The cholesterol content in immune complexes as a marker of coronary and peripheral atherosclerosis].

As many as 107 patients with coronary atherosclerosis, 66 with peripheral atherosclerosis, 27 with unaltered coronary arteries and 30 healthy blood donors were examined. The content of cholesterol in immune complexes was significantly higher in patients with coronary and peripheral atherosclerosis as compared to patients with intact arteries and healthy subjects. The highest content of cholesterol in immune complexes was detected in patients with combined lesions of coronary arteries and arteries of the lower limbs. It exceeded 3.5-5.5-fold the content of cholesterol in immune complexes in the control groups. The accuracy of the diagnosis with the aid of measuring the content of cholesterol in immune complexes in atherosclerosis of any sites was equal to 85%, in peripheral atherosclerosis to 89%, which slightly exceeded the diagnosis accuracy in atherosclerosis of coronary arteries (83%).

Adult↗