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)

Glycosphingolipids in serum and lipoproteins from Watanabe hereditable hyperlipidemic rabbit (WHHL rabbit), which is an animal model for human familial hypercholesterolemia (FH), were analyzed for the first time in this study. Chylomicrons and very low density, low density, and high density lipoproteins contained sulfatide as a major glycosphingolipid (12 nmol/mumol total phospholipids (PL) in chylomicrons, 19 nmol/mumol PL in VLDL, 18 nmol/mumol PL in LDL, and 14 nmol/mumol PL in HDL) with other minor glycosphingolipids such as glucosylceramide, galactosylceramide, GM3 ganglioside, lactosylceramide, and globotriaosylceramide. The concentration of sulfatide as a major glycosphingolipid in WHHL rabbit serum (121 nmol/ml) was much higher than that in normal rabbit serum (3 nmol/ml). Fatty acids of the sulfatides comprised mainly nonhydroxy fatty acids (C22, 23, and 24) and significant amounts of hydroxy fatty acids (about 10%) whereas long chain bases of the sulfatides comprised mostly (4E)-sphingenine with a significant amount of 4D-hydroxysphinganine (about 10%). Furthermore, sulfatides in the liver and small intestine from normal and WHHL rabbits (where serum lipoproteins are produced) were determined to amount to 260 nmol/g liver in WHHL rabbit, 104 nmol/g liver in control rabbit, 99.6 nmol/g small intestine in WHHL rabbit, and 31.2 nmol/g small intestine in control rabbit. Ceramide portions of the sulfatides in the liver were mainly composed of (4E)-sphingenine and nonhydroxy fatty acids, while those in the small intestine were mainly composed of 4D-hydroxysphinganine and hydroxy fatty acids. These results indicated that the sulfatides of serum lipoproteins were mostly derived from the liver (90% of the total), and that the remaining sulfatides (10% of the total) might be derived from the small intestine. These two sulfatides, which have different ceramide portions, could be useful markers for metabolic and biosynthetic studies of various lipoproteins in WHHL rabbit, and thus would be helpful to further elucidate the relationship between hypercholesterolemia and atherosclerosis in the rabbit.
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PMID:Occurrence of sulfatide as a major glycosphingolipid in WHHL rabbit serum lipoproteins. 366 67

Elevating fat content from 5 to 20% of diet by weight or extending the feeding period from 6 months to more than 1 year did not substantially alter the fluidity of rabbit plasma lipoprotein lipid domains. Dietary fatty acid saturation was not adequate as a predictor of lipoprotein fluidity. Rabbits fed corn oil, high in polyunsaturated fatty acid content, did not have more fluid lipoproteins than rabbits fed cocoa butter which contains a high level of saturated long chain fatty acids. Order parameters calculated from fluorescence depolarization measurements with diphenylhexatriene (DPH) showed that very low density lipoprotein (VLDL) lipids were in highly fluid or 'liquid' states at or below body temperature. Order parameter data showed transitions from ordered phase to isotropic liquid in low density lipoproteins (LDL) that were heretofore unnoted with DPH fluorescence depolarization measurements. The transition temperature was inversely related to the LDL triglyceride content, indicating probe intercalation between the fatty acyl chains of the core triacylglycerols in VLDL and LDL.
Atherosclerosis 1983 Jul
PMID:Effects of fat level, feeding period, and source of fat on lipid fluidity and physical state of rabbit plasma lipoproteins. 688 6

Epidemiological studies indicate that dietary saturated fats are implicated in coronary heart disease (CHD). Human prospective studies have shown that diets low in long chain saturated fatty acids and enriched in linoleic acid are beneficial in CHD-prevention. Experiments in animals have shown that such diets diminish atherosclerosis and the tendency to arterial thrombosis; they also lower the ability of platelets to aggregate in animals and in man. The mechanisms by which these diets produce these effects are not yet completely understood. Platelets and vascular prostaglandin-like substances may be involved as well as platelet membrane fluidity and platelet coagulant activities. On the basis of the available evidence, measures to decrease the intake of long chain saturated fatty acids (concomitant with an enhanced consumption of linoleic acid-rich products) are justified. Although certain marine oils may also have anti-thrombotic properties the possibility of undesirable side effects compels extensive investigation before their wide-spread use can be recommended.
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PMID:Dietary prevention of coronary heart disease. Effect of dietary fats on arterial thrombosis. 700 47

Cyclopropenoid compounds are derived from naturally occurring C19 long chain fatty acids which have been shown to increase mitosis in rat hepatocytes, to elevate serum cholesterol and to enhance atherosclerosis in hens. In order to study the direct effects of sterculi acid triglyceride on smooth muscle proliferation, sterculic acid triglyceride in Sterculia foetida seed oil extract was added to tissue culture media in concentrations of 2 x 10(-6) to 2 x 10(-3)mg/ml and tested on primary as well as subcultures of rabbit aorta smooth muscle cells. In stationary primary rabbit aortic smooth muscle cell cultures the outgrowth of explants treated with Sterculia foetida seed extract increased in diameter. This response was similar to the increase of cultures treated with hyperlipemic serum (which has been shown to stimulate smooth muscle cell proliferation in previous studies in this laboratory). Using autoradiography following a (3H) thymidine pulse, the percentage of labeled cells was increased in the sterculic acid triglyceride treated groups, as compared to controls. In trypsinized, subcultured rabbit aortic smooth muscle cells, Sterculia foetida seed oil extract resulted in an increased incorporation of (3H) thymidine per milligram of protein. These results, indicating increased cell proliferation, were significant at p less than 0.05.
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PMID:The mitogenic effects of methyl sterculate on aortic smooth muscle cells. 718 93

To determine whether the specificity of lecithin: cholesterol acyltransferase (LCAT) influences the susceptibility to atherosclerosis, we compared the composition and in vitro synthesis of cholesteryl ester (CE) in the plasmas of 14 vertebrate species with varying predisposition to atherosclerosis. The susceptible species (Group I) had significantly higher ratios of 16:0 CE/20:4 CE in their plasma than the resistant species (Group II). The in vitro formation of labeled CE species in native plasma from labeled cholesterol correlated highly with the mass composition, showing that the LCAT reaction is the predominant source of plasma CE in all the animal species examined. Isolated LCATs from Group I species also synthesized CE with higher ratios of 16:0/20:4 than LCATs from Group II when egg phosphatidylcholine (PC) was used as the acyl donor. In addition, the Group I LCATs exhibited lower specificity towards sn-2-20:4 and sn-2-22:6 PCs, and higher specificity towards sn-2-18:2 PC species than Group II LCATs. With 16:0-20:4 PC as the substrate, all Group I LCATs synthesized more 16:0 CE than 20:4 CE, whereas all Group II LCATs, with the exception of dog enzyme, synthesized predominantly 20:4 CE, showing that the two types of LCAT have different positional specificities towards this PC. These results suggest that there are two classes of LCAT in nature that differ from each other in their substrate and positional specificities, possibly because of differences in their active-site architectures. We propose that the presence of one type of LCAT, which cannot efficiently transfer certain long chain polyunsaturated acyl groups and which consequently synthesizes more saturated CE, may increase the risk of atherosclerosis.
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PMID:Specificity of lecithin:cholesterol acyltransferase and atherogenic risk: comparative studies on the plasma composition and in vitro synthesis of cholesteryl esters in 14 vertebrate species. 759 2

Arginine, glutamine, the long chain polyunsaturated omega-3 and omega-6 fatty acids, and, to a lesser extent, ribonucleic acid and the vitamins E, C, and A have pharmacologic effects when given in amounts in excess of what is needed to prevent nutritional deficiency. These effects are exerted primarily via the immune system, and immunoenhancing diets that embody the recently developed principles of nutritional pharmacology have been shown to reduce infectious complications by approximately 75% in surgical patients and hospital stay by more than 20% in surgical patients and patients in the intensive care unit in three independent, prospective, randomized studies, two of which were double-blinded. These findings suggest that specialized diets can be designed that will be of benefit to patients with cancer, atherosclerosis, intestinal diseases, autoimmune diseases, infections, and trauma. However, the interaction of these nutrients in pharmacologic amounts with standard pharmacologic drugs is largely unknown, as are the effects of long-term administration of specialized diets to treat these conditions.
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PMID:Immunoenhancement via enteral nutrition. 769 65

Binding of modified lipoproteins including oxidized low density lipoprotein (oxidized LDL) to cell surface receptors is an initial step of conversion of monocyte-derived macrophages into lipid-laden foam cells, a key cellular component in the early lesions of atherosclerosis. We have searched for microbial metabolites that inhibit oxidized LDL-induced lipid accumulation in macrophages and isolated three compounds from a strain of Bacillus sp. as inhibitors of oxidized LDL binding. By chemical and spectroscopic analyses, these metabolites were shown to be related to the cyclic lipopeptide iturin C. Two of these compounds were novel metabolites having long chain beta-amino acid moieties of different length. These agents, at concentrations ranging from 5 to 20 microM, inhibited cell surface binding of oxidized 125I-LDL, resulting in reduced intracellular accumulation and degradation of the lipoprotein as well as in reduced cholesteryl ester formation from [14C]oleate in macrophages J774.
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PMID:Inhibition of the binding of oxidized low density lipoprotein to the macrophages by iturin C-related compounds. 773 Jan 57

The incidence of obesity, noninsulin-dependent diabetes mellitus (NIDDM), hypertension, and coronary artery disease has increased in the developed world. At the same time, major changes in the type and amount of fatty acid intake have occurred over the past 40-50 years, reflected in increases in saturated fat (from both animal sources and hydrogenated vegetable sources), trans fatty acids, vegetable oils rich in linoleic acid, and an overall decrease in long chain polyunsaturated fatty acids (arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid--C20-C22). Recent findings that C20-C22 in muscle membrane phospholipids are inversely related to insulin resistance, whereas linoleic acid is positively related to insulin resistance, suggest that diet may influence the development of insulin resistance in obesity, insulin-dependent diabetes mellitus (IDDM), hypertension, and coronary artery disease (including asymptomatic atherosclerosis and microvascular angina). These conditions are known to have genetic determinants and have a common abnormality in smooth muscle response and insulin resistance. It is proposed that the current diet influences the expression of insulin resistance in those who are genetically predisposed. Therefore, clinical investigations are needed to evaluate if lowering or preventing insulin resistance through diet by increasing arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, while lowering linoleic acid and decreasing trans fatty acids from the diet, will modify or prevent the development of these diseases.
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PMID:Is insulin resistance influenced by dietary linoleic acid and trans fatty acids? 800 41

The elevated level of plasma low density lipoprotein (LDL) in hyperlipidemic patients is an important risk factor for the production of atherosclerosis. Plasma LDL must be modified before it can produce an impairment of endothelium-dependent relaxation in aortic rings or enhancement of uptake by macrophages. The dramatic increase in lysophosphatidylcholine (lysoPC) content in oxidatively modified LDL has been touted as an important biochemical factor for the impairment of endothelium-dependent relaxation. The present study was designed to examine the lysoPC composition of oxidized LDL samples from normal and hyperlipidemic subjects, and their effects on the impairment of endothelium-dependent relaxation. Oxidatively modified LDL from hyperlipidemic patients contained a slightly higher level (17%) of lysoPC, but produced a disproportionately greater impairment of endothelium-dependent relaxation than that from normal subjects. As lysoPC is composed of many molecular species, its composition in oxidized LDL samples was analyzed. In hyperlipidemic patients, lysoPC samples were found to contain a higher proportion of long-chain acyl groups. Subsequent studies revealed that only long-chain lysoPC (C > 16:0) were effective in impairing endothelium-dependent relaxation. Experimental loading of oxidized LDL from normal subjects with long chain lysoPC to mimic levels observed in oxidized LDL from hyperlipidemic patients resulted in further impairment of endothelium-dependent relaxation. We conclude that the greater proportion of long-chain lysoPC found in the oxidized LDL of hyperlipidemic subjects is responsible for the increased impairment of endothelium-dependent vascular relaxation. We propose that the high level of LDL found in the plasma of hyperlipidemic patients, coupled with its enhanced ability to generate long chain species of lysoPC during oxidative modification, are important factors for the development of atherosclerosis in these patients.
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PMID:Oxidative modification of low density lipoprotein in normal and hyperlipidemic patients: effect of lysophosphatidylcholine composition on vascular relaxation. 910 35

In previous studies conducted in rats and in women, we have shown that oral contraceptive (OC) administration induced a platelet hyperaggregation simultaneously with an increased platelet lipid biosynthesis which might be related to lipid peroxidation. In the present study, we specifically studied the arachidonic acid and the fibrinolytic pathways in relation to the fatty acid composition in female rats treated for 6 weeks with OC (ethinyl estradiol plus lynestrenol). We found that platelets of treated animals were not only hyper-responsive to thrombin and ADP, but also to sodium arachidonate. In addition, the results of the thrombin-induced release of labeled arachidonic acid pre-incorporated into platelet membrane phospholipids showed an increased biosynthesis of lipoxygenase and cyclooxygenase metabolites after OC treatment. These data indicated a stimulated platelet arachidonate metabolism in OC animals compared to controls which was further confirmed by the increased thrombin-induced production of thromboxane B2 (TXB2) as measured with a radioimmunoassay. The platelet thrombin-stimulated TXB2 biosynthesis was inhibited in vitro in the presence of 500 mu M aspirin and 1 mM vitamin E; the erythrocytes from OC animals compared with controls presented an enhanced in vitro susceptibility to free radical-induced hemolysis. These data indicated that a free radical mediated-process might occur. This hypothesis is confirmed by an increase of plasma lipid peroxidation parameters (conjugated dienes, lipid peroxides, thiobarbituric acid reactive substances). After OC-treatment, a decrease in plasma and platelet long chain polyunsaturated fatty acids, particularly (n-3), is in keeping with this idea. Furthermore, the results of the peritoneal macrophage-dependent fibrinolytic activity indicated that OC induced a drastic decrease in urokinase plasminogen activator activity which might further contribute to the platelet hyperactivity. Altogether these data suggest that besides the reported increase in clotting factors, platelet hyperactivity, possibly through a stimulated free radical-induced arachidonic acid metabolism, might be involved in the known high thrombogenic risk observed in OC users.
Atherosclerosis 1996 Apr 05
PMID:Enhanced platelet thromboxane synthesis and reduced macrophage-dependent fibrinolytic activity related to oxidative stress in oral contraceptive-treated female rats. 912 95


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