Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effects of high plasma cholesterol levels on platelet-vessel wall interactions under high shear rate conditions typical of the apex of stenotic arteries (2,600 sec-1). Hypercholesterolemia was induced by feeding rabbits a 0.5% cholesterol-rich diet for 60 days. Platelet deposition was studied by use of an annular perfusion chamber and de-endothelialized abdominal rabbit aortas as substrates. After ingestion of the atherogenic diet, the experimental group of animals developed severe hypercholesterolemia, platelets became more fluid as determined by steady-state fluorescence anisotropy (p less than 0.05), and red blood cell deformability was decreased (p less than 0.001) when compared with normal controls. The fatty acid composition of platelet membranes showed an increase in the percentage of the long-chain saturated fatty acids (palmitic, C16:0, and stearic, C18:0) that may account for the lower polyunsaturated/saturated fatty acid ratio observed in the hyperlipemic animals. Total platelet deposition was significantly increased (p less than 0.05) in the hyperlipemic group as compared with the control group at 5 minutes' perfusion time, becoming less evident at 20 minutes' perfusion time. Our results suggest that the presence of hyperlipidemia may contribute to acute thrombosis by enhancing platelet-vessel wall interaction.
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PMID:Platelet deposition at high shear rates is enhanced by high plasma cholesterol levels. In vivo study in the rabbit model. 199 57

Structural analyses were performed on milk fat samples obtained 3-10 days postpartum from a lactating patient with primary Type 1 hyperlipidemia. The milk triacylglycerols contained 3-7% C10, 14-21% C12, 20-30% C14, 22-26% C16 and 20-30% C18 (largely oleic) acids. Gas liquid chromatographic (GLC) analyses of the X-1,3- and X-1,2-diacylglycerols on polar siloxane columns showed a markedly non-random association of acyl chains. Stereospecific analyses indicated that the short chain length fatty acids were confined essentially to the sn-3-position of the triacylglycerol molecule. Furthermore, these acids were largely absent from the phosphatidylcholines and the endogenous sn-1,2-diacylglycerols of the milk fat. It is concluded that the short chain fatty acids are incorporated into the milk triacylglycerols during the final stage of biosynthesis via the phosphatidic acid pathway, and that the overall fatty acid distribution is consistent with the 1-random 2-random 3-random hypothesis.
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PMID:Milk fat structure of a patient with type 1 hyperlipidemia. 650 29

New isoforms of apolipoprotein (apo)C-I and apoC-III have been detected in delipidated fractions from very low density lipoprotein (VLDL) using matrix-assisted laser desorption (MALDI) and electrospray ionization (ESI) mass spectrometry (MS). The cleavage sites of truncated apoC-III isoforms have also been identified. The VLDL fractions were isolated by fixed-angle single-spin ultracentrifugation using a self-generating sucrose density gradient and delipidated using a newly developed C18 solid phase extraction protocol. Fifteen apoC isoforms and apoE were identified in the MALDI spectra and the existence of the more abundant species was verified by ESI-MS. The relative intensities of the apoCs are closely correlated in three normolipidemic subjects. A fourth subject with type V hyperlipidemia exhibited an elevated apoC-III level and a suppressed level of the newly discovered truncated apoC-I isoform. ApoC-II was found to be particularly sensitive to in vitro oxidation. The dynamic range and specificity of the MALDI assay shows that the complete apoC isoform profile and apoE phenotype can be obtained in a single measurement from the delipidated VLDL fraction.
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PMID:Mass spectral study of polymorphism of the apolipoproteins of very low density lipoprotein. 1006 43

There are findings indicating that a decreased ratio of plasma coenzyme Q10 (Q10) to LDL cholesterol could be associated with an increased risk of atherosclerosis. Furthermore, the proportion of plasma Q10H2 (reduced Q10, ubiquinol) of total Q10 has been shown to be attenuated in major diseases, such as hyperlipidemia and coronary artery disease. These observations suggest that measurement of plasma total Q10 and the proportion of plasma Q10H2 of total Q10 would be of clinical significance. However, epidemiological studies addressing this issue require large numbers of subjects, and measurements from unfrozen samples are unfeasible. For this reason, we evaluated the stability of Q10 samples during sample storage and processing. We also compared solid phase and hexane pre-treatments prior to high-performance liquid chromatographic determination of Q10. Our results indicate that samples for plasma total Q10 measurement can be pre-treated in normal laboratory lighting conditions, thawed and frozen several times, and stored deep frozen for a couple of years without changes in measured Q10 values. If purification of the samples by silica and C18 is needed, the best reproducibility tends to be achieved with powder treatment (not with cartridges). However, to measure successfully the proportion of plasma ubiquinol of total Q10, samples must be thawed, extracted, and analysed one at a time and quickly to ensure minimal ubiquinol oxidation during the measurement process.
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PMID:Measurement and stability of plasma reduced, oxidized and total coenzyme Q10 in humans. 1061 57

In this study, we investigated the hypolipidemic action of eicosapentaenoic acid (EPA) and its mechanism. Three types of 5% fat diets (stearic acid, linoleic acid, and EPA) were prepared in our laboratory. Rats that weighed 170-190 g were fed one of these diets for 20 weeks at an equivalent calorie value (groups S, L, and E). Weight gain occurred in the following order: group E < group S < group L. Serum levels of total cholesterol, triglycerides, phospholipids and total lipids were significantly lower in group E than in the other groups. Analysis of the fatty acid composition of adipose tissue showed that the level of C18:1 was significantly higher in group S, that of C18:2 was significantly higher in group L, and that of C16:0 was significantly higher in group E than in the other groups. These results indicated that EPA had a hypolipidemic action, higher ketogenicity, and lower lipogenicity than the other fatty acids. Inclusion of EPA in the diet of hyperlipidemic subjects may thus help in the primary prevention of hyperlipidemia and, in turn, morbid obesity.
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PMID:Effects of Eicosapentaenoic Acid on Lipid Metabolism in Obesity Treatment. 1077 11

Aromatase (CYP19) is a cytochrome P450 enzyme that catalyzes the formation of aromatic C18 estrogens from C19 androgens. It is expressed in various tissues and contributes to sex-specific differences in cellular metabolism. We have generated aromatase-knockout (ArKO) mice in order to study the role of estrogen in the regulation of glucose metabolism. The mean body weights of male ArKO (-/-) mice (n=7) and wild-type littermates (+/+) (n=7) at 10 and 12 weeks of age were 26.7+/-1.9 g vs 26.1+/-0.8 g and 28.8+/-1.4 g vs 26.9+/-1.0 g respectively. The body weights of the ArKO and wild-type mice diverged between 10 and 12 weeks of age with the ArKO males weighing significantly more than their wild-type littermates (P<0.05). The ArKO males showed significantly higher blood glucose levels during an intraperitoneal glucose tolerance test compared with wild-type littermates beginning at 18 weeks of age. By 24 weeks of age, they had higher fasting blood glucose levels compared with wild-type littermates (133.8+/-22.8 mg/dl vs 87.8+/-20.3 mg/dl respectively; P<0.01). An intraperitoneal injection of insulin (0.75 mU insulin/g) caused a continuous decline in blood glucose levels in wild-type mice whereas ArKO males at 18 weeks and older exhibited a rebound increase in glucose levels 30 min after insulin injection. Thus, ArKO male mice appear to develop glucose intolerance and insulin resistance in an age-dependent manner. There was no difference in fasting serum triglyceride and total cholesterol levels between ArKO male mice and wild-type littermates at 13 and 25 weeks of age. However, serum triglyceride and cholesterol levels were significantly elevated following a meal in ArKO mice at 36 weeks of age. Serum testosterone levels in ArKO male mice were continuously higher compared with wild-type littermates. Treatment of ArKO males with 17beta-estradiol improved the glucose response as measured by intraperitoneal glucose and insulin tolerance tests. Treatment with fibrates and thiazolidinediones also led to an improvement in insulin resistance and reduced androgen levels. As complete aromatase deficiency in man is associated with insulin resistance, obesity and hyperlipidemia, the ArKO mouse may be a useful animal model for examining the role of estrogens in the control of glucose and lipid homeostasis.
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PMID:Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency. 1255 72

Lipoprotein(a) [Lp(a)] is considered a risk factor for coronary heart disease. Our aim was to investigate the effect of individual fatty acids on postprandial plasma Lp(a) and its association with lipemia and tissue plasminogen activator (t-PA). Five test fats dominated by (approximately 43% g/kg) stearic (S), palmitic (P), oleic, C18:1 trans (T), or linoleic acid were produced by interesterification. Sixteen young healthy men were served the individual test fats incorporated into meals (1g fat/kg body wt) after a 12-h fast in random order on different days, separated by 3-wk washout periods. Blood samples were drawn before and 2, 4, 6, and 8 h after eating. There was a pronounced increase in Lp(a) concentrations after intake of the test meals, and the test fats resulted in a difference in Lp(a) response (P < 0.001; diet x time interaction). However, T fat did not change Lp(a) during the time course studied. T fat resulted in less area under the plasma Lp(a) concentration curve compared to S and P fat (P </= 0.003). Test fat with saturated fatty acids resulted in the highest Lp(a) and lowest plasma triacylglycerol (TAG) response, with the reversed situation for T fat. There was no association between Lp(a) and t-PA. In conclusion, intake of meals high in individual dietary fatty acids increased postprandial plasma Lp(a) differently. There seems to be a complex regulatory role of plasma TAG on nonfasting plasma Lp(a) concentrations.
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PMID:Postprandial lipoprotein(a) is affected differently by specific individual dietary fatty acids in healthy young men. 1546 46

Epidemiologic studies have shown a beneficial association between polyunsaturated fatty acid (PUFA), specifically linoleic acid (C18:2, n-6), intake and cardiovascular disease morbidity and mortality. Clinical studies have shown that n-6 PUFAs have the most potent cholesterol-lowering effects of the individual fatty acid classes, and emerging evidence suggests that PUFAs have favorable effects on postprandial lipemia. However, some studies suggest that high intakes of linoleic acid may have adverse effects on proinflammatory cytokines and adhesion molecules. Research is needed to establish the optimal level of dietary PUFAs that maximally affects the greatest number of health risk factors.
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PMID:Polyunsaturated fatty acids and cardiovascular health. 1562 14

Plasma lipid composition, platelet aggregation, cholesterol (Ch)/glycoprotein IIb-IIIa (GP) and phospholipid (Ph)/GP molar ratios, fatty acid composition and structural order (1, 6-diphenyl-1, 3, 5-hexatriene (DPH) fluorescence anisotropy at 35 degrees C (r(DPH,35)) of human platelet plasma membranes (HPPM) were measured in four DPH,35 groups of hyperlipidemic patients (II: plasma Ch < 250 mg/dl and TG (triglycerides) <220 mg/dl, n = 21; III: Ch > 250 mg/dl and TG < 220 mg/dl, n = 23; IV: Ch < 250 mg/dl and TG > 220 mg/dl, n = 18; and V: Ch > 250 mg/dl and TG > 220 mg/dl, n = 12) and compared with those of the control group (I). Our results were: (i) in groups III, IV and V the HPPM (Ch + Ph)/GP molar ratio increased 7.0+/-7.7% (mean SD); (ii) the Ph/GP molar ratio increased significantly in groups III, IV and V, but most in IV and V, while the Ch/GP molar ratio increased only in groups III and V; (iii) the mean relative increase of Ch with respect to Ph in the HPPM of groups III, IV and V was 140% 21% and 54%, respectively; (iv) the Ch/GP molar ratio was correlated with LDL-Ch (0.41+/-0.16, P < 0.002, n = 55, for all the subjects and 0.60+/-0.11, P < 2.10(-4), n = 33, for subjects with TG < 220 mg/dl), however, it was totally uncorrelated with HDL-Ch; (v) the HPPM Ch/Ph molar ratio was positively correlated with plasma Ch (r = 0.51+/-0.08, P < 1.10(-6), n = 83) and with (LDL + HDL) Ch (r = 0.64+/-0.07, P < 1.10(-6), n = 73), the former correlation increased significantly ( r = 0.67+/-0.07, P < 1.10(-6), n = 53) when done only for subjects with TG < 220 mg/dl; (vi) the Ch/Ph molar ratio was only increased in group III (0.70+/-0.03, P < 3.10(-5), n = 23) and decreased in group IV (0.62+/-0.02, P < 0.001, n = 18); (vii) the fatty acid/GP molar ratio was significantly increased in groups IV and V, however, a significant absolute and relative increase of C16:0 and C18:1 was observed only in severe hypertriglyceridemia (> 500 mg/dl), together with a relative decrease of C18:0 and C20:4 ( n - 6); (viii) the HPPM structural order, as probed by r(DPH,35), was negatively correlated with DPH,35 plasma TG (r =- 0.61+/-0.10, P < 4.10(-5), n = 39), the Ph/GP molar ratio (r =-0.58+/-0.10, P < 2.10(-4), n = 39) and the the (C18:1 + C18:2))/GP molar ratio (r =- 0.80+/-0.05, P < 1.10(-6), n = 39), however, it was independent of plasma and HPPM Ch; (ix) the higher HPPM Ch/Ph molar ratio in group III was associated (r = 0.58+/-0.12, P < 0.005, n = 22) with a moderately higher platelet reactivity to collagen. We conclude that Ch and Ph were distinctly incorporated to HPPM in the different groups of hyperlipidemia and, therefore, that the absolute increase of Ch and Ph was more informative to understand the structural and functional modifications of the HPPM in hyperlipidemias, than the Ch/Ph molar ratio. On the other hand, the r was sensitive to the DPH,35 increase in the content of HPPM Ph and C18:1 + C18:2 and it was insensitive to the increase in the Ch content.
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PMID:Distinct cholesterol and phospholipid incorporation at the platelet plasma membrane of hyperlipidemic subjects: structural order and function. 1679 20

Effects of different fatty acids on the development of hepatic steatosis were studied in rats receiving total parenteral nutrition (TPN). 65 rats, with internal jugular catheters, were divided into one control group (n = 8), and four experimental groups (n = 13-15 each). The control group was fed a chow diet and all experimental groups received TPN. TPN provided 300 kcal/kg/day with 40% of the non-protein energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fatty acid composition of the fat emulsion. Four kinds of fat emulsions rich in: 1) medium chain fatty acids (C8:0,C10:0), 2) oleic acid (C18:1 n-9), 3) linoleic acid (C18:2 n-6), 4) eicosapentaenoic acid (C20:5 n-3)/docosahexaenoic acid (C22:6 n-3), were used. These fat emulsions were prepared with: 1) a mixture of medium chain triglycerides (MCT) and soybean oil (9:1), 2) olive oil, 3) safflower oil, 4) fish oil, respectively. The results of the study demonstrated a higher hepatic lipid content in the olive oil and safflower oil groups than in the control group, whereas no significant difference was seen between the MCT and control groups. Also, no difference was observed between the fish oil and control groups. With regard to the plasma lipids, the MCT group and olive oil group produced hyperlipidaemia. The plasma of the safflower oil and fish oil groups, however, had a low lipid concentration comparable to the control group. These results suggest that TPN with a fat emulsion prepared with fish oil does not cause hyperlipidaemia nor induce hepatic steatosis in normal rats.
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PMID:Effects of fat emulsions with different fatty acid composition on plasma and hepatic lipids in rats receiving total parenteral nutrition. 1684 91


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