Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review discusses the role of three mediators, synthesized by vascular endothelial cells, that help to keep the surface of the normal endothelium nonthrombogenic. The first is prostacyclin, a product of arachidonic acid metabolism discovered in 1976. This labile prostanoid, with a half-life of approximately 3 minutes, relaxes vascular smooth muscle and inhibits the aggregation of blood platelets. Prostacyclin and its analogues are currently being tested clinically for use in cardiovascular diseases such as primary pulmonary hypertension. The second mediator discussed is endothelium-derived relaxing factor (EDRF), discovered in 1980, which also relaxes smooth muscle and inhibits the aggregation and adhesion of platelets. Substances that stimulate the release of EDRF include acetylcholine, bradykinin, and adenosine 5'-diphosphate. EDRF is even more labile than prostacyclin, with a half-life of about 6 seconds, and it has recently been identified as nitric oxide. Prostacyclin and EDRF are released together following stimulation of endothelial receptors and synergize to inhibit platelet aggregation. 13-Hydroxy-9,11-octadecadienoic acid, a third suggested mediator, is not released but acts from inside the cell to make the endothelial surface nonadhesive for circulating blood cells. It is proposed that these three mediators form the endothelial defense mechanism against blood-borne cells and chemicals and that breakdown of this barrier results in diseases such as hypertension and atherosclerosis.
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PMID:Mediators produced by the endothelial cell. 306 Apr 28

Conjugated linoleic acid (CLA) consists of a series of positional and geometric dienoic isomers of linoleic acid that occur naturally in foods. CLA exhibits antioxidant activity in vitro and in vivo. To assess the effect of CLA on atherosclerosis, 12 rabbits were fed a semi-synthetic diet containing 14% fat and 0.1% cholesterol for 22 weeks. For 6 of these rabbits, the diet was augmented with CLA (0.5 g CLA/rabbit per day). Blood samples were taken monthly for lipid analysis. By 12 weeks total and LDL cholesterol and triglycerides were markedly lower in the CLA-fed group. Interestingly, the LDL cholesterol to HDL cholesterol ratio and total cholesterol to HDL cholesterol ratio were significantly reduced in CLA-fed rabbits. Examination of the aortas of CLA-fed rabbits showed less atherosclerosis.
Atherosclerosis 1994 Jul
PMID:Conjugated linoleic acid and atherosclerosis in rabbits. 798 Jul 4

Conjugated linoleic acid is a collective term used to designate a mixture of positional and geometric isomers of linoleic acid in which the double bonds are conjugated. Unlike linoleic acid, there is a paucity of information regarding the effect of dietary conjugated linoleic acid on plasma lipoproteins and aortic atherosclerosis. Therefore, fifty hamsters were divided into five groups of ten and fed 0 (Control), 0.06 (LOW), 0.11 (MEDIUM), and 1.1 (HIGH) en% conjugated linoleic acid or 1.1 en% linoleic acid. Blood samples were taken at 4, 8 and 11 weeks for plasma lipid analyses and for plasma tocopherol assay at sacrifice. Animals fed the conjugated linoleic acid-containing diets collectively had significantly reduced levels of plasma total cholesterol, non-high density lipoprotein cholesterol, (combined very low and low density lipoprotein) and triglycerides with no effect on high density lipoprotein cholesterol, as compared to CONTROLs. Linoleic acid-fed animals relative to CONTROLs also had reduced plasma total cholesterol, non-high density lipoprotein cholesterol and triglycerides, but only the latter was statistically significant. Compared to the CONTROL group, plasma tocopherol/total cholesterol ratios determined from plasma pools for the LOW, MEDIUM and HIGH conjugated linoleic acid and linoleic acid groups were increased by 48%, 48%, 86% and 29%, respectively, suggesting a tocopherol-sparing effect, at least for the conjugated linoleic acid treatment. Morphometric analysis of aortas revealed less early atherosclerosis in the conjugated linoleic acid and linoleic acid-fed hamsters compared to the CONTROL group.
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PMID:Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters. 920 99

Linoleic acid is the most abundant fatty acid in human low density lipoproteins (LDL). Oxidation of LDL transforms linoleic acid to hydroperoxyderivatives. These are converted to 9-hydroxy-10,12-octadecadienoic acid (9-HODE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODE). 9-HODE is much more abundant in oxidized LDL than other lipid peroxidation products and therefore an indicator of lipid peroxidation (LPO). In this study the 9-HODE content in the LDL of 19 obviously healthy volunteers and 17 atherosclerotic patients was investigated. The level of 9-HODE obtained from LDL of young atherosclerotic patients (aged 36-47 years) was increased by a factor of 20 when compared with samples from healthy volunteers of the same age group. The content of 9-HODE in the LDL of atherosclerotic patients aged between 69 and 94 years increased 30-100 fold when compared with young healthy individuals, but when compared with 'healthy' individuals of the same age group it was only 2-3 fold increased. Obviously, as individuals grow older LDL becomes more and more oxidized. Consequently, assuming that LDL oxidation is a precondition for atherosclerosis--older individuals will suffer from atherosclerosis, even if no easy detectable visible signs of this disease are recognizable. According to 9-HODE determination, the onset of the disease starts slowly in most individuals at around 50 years of age.
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PMID:Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients. 948 97

Catalytic amounts of Fe2+ or Fe3+ ions are widely applied to induce simulated biological lipid peroxidation reactions. Independently, whether Fe2+ or Fe3+ were used, similar products were obtained. We show in this paper that the product spectrum is indeed very different, whether one ion species, either Fe2+ or Fe3+, is present in excess; thus, decomposition of (13S,9Z,11E) 13-hydroxyperoxy-9, 11-octadecadienoic acid (13S-HPODE) generates in the presence of equimolar amounts of Fe2+ ions mainly the corresponding alcohol (13S, 9Z,11E) 13-hydroxy-9,11-octadecadienoic acid besides 12,13-epoxy-11-hydroxy-9-octadecenoic acid (12,13-epHOD) and 13-oxo-9,11-octa-decadienoic acid (13-KODE), while decomposition of 13S-HPODE with equimolar amounts of Fe3+ produces mainly 12,13-epHOD, hydrolysis products thereof and other oxidized products, e.g., hydroxyoxo acids. In addition, unusually large amounts of aldehydes are formed, e.g., the amount of 4-hydroxy-nonenal was found to exceed that obtained by Fe2+ induced air oxidation for a factor of about 100. Since these further oxidation products are suspected to cause cell damage, liberated Fe3+ ions seem to be responsible for generation of toxic products in inflammatory diseases, e.g., atherosclerosis.
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PMID:Strong dependence of the lipid peroxidation product spectrum whether Fe2+/O2 or Fe3+/O2 is used as oxidant. 959 8

Conjugated linoleic acid (CLA) has been shown to inhibit carcinogenesis and atherosclerosis, enhance immunologic function while protecting against the catabolic effects of immune stimulation, affect body composition change (reducing body fat gain while enhancing lean body mass gain), and stimulate the growth of young rats. We discuss possible biochemical mechanisms that underlie these physiological effects. We emphasize the importance of considering the effects, both individually and combined, of the two CLA isomers (cis-9, trans-11 CLA and trans-10, cis-12 CLA) that have been shown to exhibit biological activity and which appear to exert their effects via different biochemical mechanisms.
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PMID:Mechanisms of action of conjugated linoleic acid: evidence and speculation. 1063 56

Various forms of oxidized low-density lipoproteins (Ox-LDL) are thought to play a major role in the development of atherosclerosis. The lipid components of Ox-LDL present a plethora of proatherogenic effects in in vitro cell culture systems, suggesting that oxidative stress could be an important risk factor for coronary artery disease. However, buried among these effects are those that could be interpreted as antiatherogenic. The present study demonstrates that various oxidants, including oxidized fatty acids and mildly oxidized forms of LDL (MO-LDL), are able to induce catalase (an antioxidant enzyme) expression in rabbit femoral arterial smooth muscle cells (RFASMC), RAW cells (macrophages), and human umbilical vein endothelial cells (HUVEC). In RFASMC, catalase protein, mRNA, and the enzyme activity are increased in response to oxidized linoleic acid (13-hydroperoxy-9,11-octadecadienoic acid [13-HPODE] and 13-hydroxy-9,11-octadecadienoic acid [13-HODE]), MO-LDL, or hydrogen peroxide (H(2)O(2)). Such an increase in catalase gene expression cannot totally be attributed to the cellular response to an intracellular generation of H(2)O(2) after the addition of 13-HPODE or 13-HODE because these agents induce a further increase of catalase as seen in catalase-transfected RFASMC. Taken together with the induction of heme oxygenase, NO synthase, manganese superoxide dismutase (Mn-SOD), and glutathione synthesis by oxidative stress, our results provide yet more evidence suggesting that a moderate oxidative stress can induce cellular antioxidant response in vascular cells, and thereby could be beneficial for preventing further oxidative stress.
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PMID:Lipid peroxides induce expression of catalase in cultured vascular cells. 1094 7

Conjugated linoleic acid (CLA) is a collective term for positional and geometric isomers of octadecadienoic acid in which the double bonds are conjugated, i.e. contiguous. CLA was identified as a component of milk and dairy products over 20 years ago. It is formed as an intermediate in the course of the conversion of linoleic acid to oleic acid in the rumen. The predominant naturally occurring isomer is the cis-9, trans-11 modification. Treatment of linoleic acid-rich oils such as safflower oil, soybean oil, or maize oil with base and heat will result in the formation of CLA. Two isomers predominate in the synthetic preparation, c9,t11 and t10,c12. CLA has been shown to inhibit chemically-induced skin, stomach, mammary or colon tumours in mice and rats. The inhibition of mammary tumours in rats is effective regardless of type of carcinogen or type or amount of dietary fat. CLA has also been shown to inhibit cholesterol-induced atherosclerosis in rabbits. When young animals (mice, pigs) are placed on CLA-containing diets after weaning they accumulate more body protein and less fat. Since CLA is derived from the milk of ruminant animals and is found primarily in their meat and in products derived from their milk there is a concerted world-wide effort to increase CLA content of milk by dietary means. Its effect on growth (less fat, more protein) is also a subject of active research. The mechanisms underlying the effects of CLA are still moot.
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PMID:Antimutagenic and some other effects of conjugated linoleic acid. 1095 69

Milk is often seen as a potential promotor of atherosclerosis and coronary heart disease because it is a source of cholesterol and saturated fatty acids. But there are several studies indicating that milk and milk products may not affect adversely blood lipids as would be predicted from its fat content and fat composition. There are even factors in milk and milk products which may actively protect from this condition by improving several risk factors. Calcium, bioactive peptides and as yet unidentified components in whole milk may protect from hypertension, and folic acid, vitamin B6 (pyridoxine) and B12 (cyanocobalamin) or other unidentified components of skim milk may contribute to low homocysteine levels. Conjugated linoleic acid may have hypolipidaemic and antioxidative and thus antiatherosclerotic properties. Epidemiological studies suggest that milk and milk products fit well into a healthy eating pattern emphasizing cereals and vegetables.
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PMID:Bioactive substances in milk with properties decreasing risk of cardiovascular diseases. 1124 60

Conjugated linoleic acid (CLA) has been suggested by some animal studies to possess antiatherogenic properties. To determine, in humans, the effect of dietary CLA on blood lipids, lipoproteins, and tissue fatty acid composition, we conducted a 93-d study with 17 healthy female volunteers at the Metabolic Research Unit of the Western Human Nutrition Research Center. Throughout the study, subjects were fed a low-fat diet [30 energy percent (en%) fat, 19 en% protein, and 51 en% carbohydrate] that consisted of natural foods with the recommended dietary allowances for all known nutrients. After a 30-d stabilization period, subjects were randomly assigned to either an intervention group (n = 10) supplemented daily with capsules containing 3.9 g of CLA or a control group (n = 7) that received an equivalent amount of sunflower oil. The CLA capsules (CLA 65%) contained four major cis/trans geometric isomers (11.4% 9 cis-,11 trans-18:2; 10.8% 8 trans-,10 cis-18:2; 15.3% 11 cis-,13 trans-18:2; and 14.7% 10 trans-,12 cis-18:2) and their corresponding cis/cis (6.74% total) and trans/trans (5.99% total) varieties in smaller amounts. Fasting blood was drawn on study days 30 (end of the stabilization period), 60 (midpoint of the intervention period), and 93 (end of the intervention period). Adipose tissue samples were taken on days 30 and 93. CLA supplementation for 63 d did not change the levels of plasma cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides. The weight percentage of CLA in plasma increased from 0.28 +/- 0.06 to 1.09 +/- 0.31 (n = 10, P < 0.05) after the supplementation. The 9 cis-,11 trans-isomer was the most prominent variety followed by the 11 cis-,13 trans- and 10 trans-,12 cis-isomers in lesser amounts. CLA in adipose tissue was not influenced by the supplementation (0.79 +/- 0.18 to 0.83 +/- 0.19 wt%) (n = 10) and the 9 cis-,11 trans-variety was the only isomer present. Thus, contrary to findings from some animal studies, CLA does not seem to offer health benefits, in the short term, regarding the prevention of atherosclerosis in humans. CLA supplementation for 2 mon did not alter the blood cholesterol or lipoprotein levels of healthy, normolipidemic subjects. The supplementation did increase CLA in the plasma but only 4.23% of the ingested CLA was present in the plasma at any given time. No adverse effect of CLA supplementation was detected in this study.
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PMID:The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans. 1133 77


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