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)

In a study of 100 unselected patients forty years of age or older, routine CT of the thorax demonstrated coronary artery calcification in 41%. Calcification of the left anterior descending was most common, occurring in 34%. For patients 60 years of age and over, clinical evidence of coronary artery disease was 1.7 times more common in those with calcification compared to those without; however, for patients under 60, coronary artery disease was 5.5 times more common in those with calcification than those without. Because of the strong relationship that is known to exist between coronary artery calcification and coronary arteriosclerosis, we believe that the incidental discovery of coronary artery calcification on routine CT of the thorax has significance. All patients under 60 with coronary artery calcification discovered on CT should be investigated for hyperlipidemia if this has not been done, and, if they are not known to have a history of coronary artery disease, they should have a stress test and, if positive, arteriography may be warranted.
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PMID:Coronary artery calcification identified by CT in patients over forty years of age. 271 92

Because there are no characteristic clinical or biochemical manifestations, the heterozygote state for lipoprotein lipase (LPL) deficiency has been difficult to detect. Measurements of postheparin plasma LPL activity and of LPL mass were performed in six families of probands with LPL deficiency to characterize the heterozygote state. LPL mass was measured in a sandwich enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody (5D2) that had been produced against bovine milk LPL. Thirteen obligate heterozygotes from these families had reduced LPL activity and mass below the 95th percent confidence limits of 34 normal controls, while one obligate heterozygote had LPL activity and mass between the 90th and 95th percent confidence limits. Potential heterozygotes in these families were identified as normal (n = 8) or heterozygotes (n = 6) by comparison to the 95th percent confidence limits of the controls. Some relatives in four of the six families exhibited mild hyperlipidemia, similar to the pattern seen in familial combined hyperlipidemia (FCHL). The hyperlipidemia segregated with the heterozygote state for LPL deficiency in these families (p less than 0.03). High density lipoprotein (HDL) cholesterol was significantly reduced in the heterozygotes for LPL deficiency (p less than 0.01). The measurement of LPL activity and mass allows identification of the heterozygote state for LPL deficiency, which is characterized by variable expressions of hyperlipidemia and reduced HDL cholesterol. These results suggest that the heterozygote state for LPL deficiency may form one subset of FCHL.
Arteriosclerosis
PMID:Detection and characterization of the heterozygote state for lipoprotein lipase deficiency. 271 95

Human coronary saphenous vein bypass grafts develop atherosclerosis more readily than do grafts made of internal mammary artery. The reasons for this increased susceptibility, particularly in the presence of hyperlipidemia, are not known. In this study in rabbits, we investigated the possibility that the increased susceptibility might be attributed to increased smooth muscle proliferation and foam cell accumulation in vein grafts compared to native artery. Hypercholesterolemic and control rabbits underwent placement of jugular vein grafts in the carotid artery. Dietary cholesterol content was adjusted to maintain serum cholesterol levels of 200 to 600 mg/dl in the fat-fed rabbits. The vein graft intimal thickness in hypercholesterolemic rabbits was greater than in normolipemic rabbits at 3 and 6 months after implant. The increased thickness in the hypercholesterolemic group was largely accounted for by an accumulation of lipid-laden macrophages. Medial thicknesses increased during the first month, remained constant at later times, and were similar in control and hypercholesterolemic animals. In both groups, endothelial and smooth muscle cell proliferation (thymidine labeling) increased immediately after graft implantation and declined at 3 and 6 months. No incremental mitogenic stimulus could be attributed to the hypercholesterolemia. In immunohistochemical preparations, the large foam cells were noted to be macrophages, and the intimal proliferating cells, to be smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Arteriosclerosis
PMID:Atherosclerosis in rabbit vein grafts. 271 97

Treatment with probucol, a widely used lipid-lowering agent, is associated with a significant reduction of high density lipoprotein (HDL) cholesterol levels, but with an apparently improved removal of cholesteryl esters from tissues (e.g., from tendon xanthomas). The effects of probucol (500 mg twice daily) on HDL subfraction distribution and cholesteryl ester transfer activity were tested in 12 patients with stable type II hyperlipidemia [low density lipoprotein (LDL) cholesterol greater than 180 mg/dl] after a placebo-controlled cross-over trial. Probucol significantly lowered total cholesterol (-13.8%), LDL cholesterol (-9.1%), and HDL cholesterol (-30%). By rate zonal ultracentrifugation, a marked reduction of HDL2 cholesterol (-68%) was shown, whereas changes in HDL3 were less significant (-21%). These findings were confirmed by polyacrylamide gradient gel electrophoresis, typically showing a reduction or disappearance of HDL2b particles and the prevalence of particles in the HDL3a range. Cholesteryl ester transfer from HDL to lower density lipoproteins was significantly increased (30%) in all patients. These findings suggest that, in addition to the well-documented in vitro changes (prevention of LDL peroxidation and macrophage uptake), probucol characteristically modifies HDL particle distribution in vivo, and is associated with a significant increase of cholesteryl ester transfer activity.
Arteriosclerosis
PMID:Mechanisms of HDL reduction after probucol. Changes in HDL subfractions and increased reverse cholesteryl ester transfer. 275 76

Omega-3 fatty acids have been shown to lower plasma cholesterol and triglyceride concentrations in humans. However, the effects of these fatty acids on the interactions among lipid concentrations, platelet activity, and atherogenesis have not been characterized in humans or in animals with low density lipoprotein (LDL) receptor deficiencies. To test the hypothesis that omega-3 fatty acids exert a protective effect in LDL receptor-deficient animals by lowering hyperlipidemia, reducing platelet aggregation, and reducing the severity of atherosclerosis, we evaluated young homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits that were fed omega-3 fatty acids. One-month-old male and female WHHL rabbits were placed on either a control diet (standard laboratory rabbit chow) or a diet supplemented with Menhaden fish oil (MFO), which contained eicosapentaenoic acid (EPA). Consumption measurements during the 5 months of the study indicated that the MFO-fed group received 150 to 200 mg/kg/day of EPA. Six-month-old, MFO-fed, female WHHL rabbits had significantly lower plasma concentrations of total cholesterol (582 +/- 20 mg/dl vs. 856 +/- 44 mg/dl, control, p less than 0.05) and triglycerides (266 +/- 21 mg/dl vs. 459 +/- 15 mg/dl, control, p less than 0.05), with lower serum/plasma lipoprotein concentrations [very low density lipoprotein (VLDL), LDL, high density lipoprotein (HDL)] compared to control female WHHL rabbits. Male MFO-fed rabbits had only significantly lower VLDLs (46 +/- 9 mg/dl) compared to control male WHHL rabbits (156 +/- 9 mg/dl, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Arteriosclerosis
PMID:Effect of dietary omega-3 fatty acid on serum lipids, platelet function, and atherosclerosis in Watanabe heritable hyperlipidemic rabbits. 275 81

Alimentary lipemia stimulates the transfer of cholesteryl ester between lipoproteins in vitro and may alter lipoprotein cholesteryl ester distribution in vivo. The effect of a single, large oral fat load on lipoprotein cholesteryl ester redistribution and the activity of cholesteryl ester transfer protein was investigated in six normolipidemic men (Group A), six combined hyperlipidemic men (Group B), and six hypercholesterolemic men (Group C). Fasting triglyceride-rich lipoprotein cholesteryl ester was high in Group B, low in Group A, and intermediate in Group C (A less than C less than B, p less than 0.05). After an oral fat load, total plasma cholesteryl ester was unchanged in all groups. In Group A, cholesteryl ester increased in smaller triglyceride-rich lipoproteins and remained so at 24 hours. Conversely, low density and high density lipoprotein cholesteryl ester decreased and returned to fasting values at 24 hours. In Group B, cholesteryl ester increased in large triglyceride-rich lipoproteins. Low density and high density lipoprotein cholesteryl ester (expressed as percentage of plasma cholesteryl ester) decreased. By contrast, in Group C, triglyceride-rich lipoprotein and low density lipoprotein cholesteryl ester remained unaltered, and only high density lipoprotein cholesteryl ester decreased. The activity of cholesteryl ester transfer protein increased in all groups and returned to fasting values at 24 hours. No differences in response were observed among the three groups. It is concluded that an oral fat load can induce a shift in lipoprotein cholesteryl ester distribution from high and low density lipoproteins to triglyceride-rich lipoproteins without affecting total plasma cholesteryl ester.(ABSTRACT TRUNCATED AT 250 WORDS)
Arteriosclerosis
PMID:Alimentary lipemia-induced redistribution of cholesteryl ester between lipoproteins. Studies in normolipidemic, combined hyperlipidemic, and hypercholesterolemic men. 278 75

An underlying cause of type III hyperlipoproteinemia is the presence of variant forms of apolipoprotein (apo) E that are defective in binding to apo B,E low density lipoprotein receptors. This disorder is associated almost exclusively with the apo E2/2 phenotype. However, structural and functional heterogeneity have been demonstrated within this phenotype. The apo E2(Arg158----Cys) variant, displaying 1% of normal apo E3 binding activity, is the most defective known form. In this study, we describe a method in which a pair of 19-mer synthetic oligonucleotide probes were used to distinguish between DNA coding for arginine or cysteine at position 158 in apo E. The specificity of the probes was demonstrated by using DNA from subjects whose apo E protein sequence or phenotype was known. The probes were used to screen a French-Canadian population of 34 apo E2/2 subjects to determine the frequency of the apo E2(Arg158----Cys) variant. All 34 subjects, most of whom displayed clinical or biochemical features of type III hyperlipoproteinemia, were found to be homozygous for apo E2(Arg158----Cys), strongly suggesting that this variant is the most common form of apo E2 within this ethnic and clinical population. In addition, the utility of this approach in detecting new apo E mutants was demonstrated when DNA from one of the apo E3/3 control subjects, whose family has a history of hyperlipidemia and coronary artery disease, reacted with both probes. This result suggests that this subject is heterozygous for normal apo E3 and a new apo E3 variant that is likely to be functionally equivalent to apo E2(Arg158----Cys).
Arteriosclerosis
PMID:Apolipoprotein E2(Arg158----Cys) frequency in a hyperlipidemic French-Canadian population of apolipoprotein E2/2 subjects. Determination by synthetic oligonucleotide probes. 291 21

Lymphocyte proliferation stimulated by mitogenic lectins is dependent on exogenously supplied cholesterol when endogenous cholesterol synthesis is blocked with the specific inhibitor mevinolin. Lymphocytes from patients homozygous for familial hypercholesterolemia (FH) lack low density lipoprotein (LDL) receptors, and, therefore, these patients cannot use LDL cholesterol to support proliferation when endogenous sterol synthesis is blocked. Thus, LDL receptors are required for the uptake of exogenous lipoprotein cholesterol by proliferating lymphocytes. As a result, the number of functional receptors can be assessed when endogenous sterol synthesis is inhibited and when limiting concentrations of LDL are employed to support lymphocyte proliferation. Lymphocytes from patients heterozygous for LDL receptor abnormalities can be distinguished from normal lymphocytes since the former require twice the concentration of LDL for proliferation. By contrast, in hyperlipidemia not caused by FH, lymphocyte LDL receptor activity is normal, indicating that plasma cholesterol levels do not account for abnormalities in LDL receptor function assayed in this way. Therapy with cholesterol-lowering drugs, however, can alter lymphocyte LDL receptor activity in patients with heterozygous FH. Patients with heterozygous FH respond to therapy with mevinolin and a bile-acid-binding resin by lowering plasma cholesterol levels. In some patients, treatment with cholesterol-lowering plasma cholesterol levels. In some patients, treatment with cholesterol-lowering plasma cholesterol agents is also associated with normalization of functional lymphocyte LDL receptor activity, thereby providing direct evidence that therapy can alter LDL receptor expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Arteriosclerosis
PMID:Identification of low density lipoprotein receptor abnormalities by assaying functional receptors on proliferating lymphocytes. 291 32

To develop experimental fatty liver, Wistar male rats were fed a high fat, high cholesterol (Cho) diet for 6 weeks after which their diet was changed to standard chow. The animals were then divided by random selection into a sedentary group (SG) and four treadmill exercise groups for 6 weeks as follows: walking group (WG, 10 m/min, 60 min); low-speed running group (LRG, 20 m/min, 30 min); middle-speed running group (MRG, 30 m/min, 20 min) and high-speed running group (HRG, 40 m/min, 15 min). The serum concentration of very low density lipoprotein (VLDL) and low density lipoprotein (LDL)-Cho decreased, and high density lipoprotein (HDL)-Cho increased in WG compared with the other three exercise groups. Hepatic triglyceride (TG) was significantly lower (P less than 0.05) in WG than in SG. Hepatic Cho was lower in HRG than in the other three exercise groups, and Cho in the aortic wall was higher. The results suggest that light exercise, such as walking might be more beneficial to lipid-lipoprotein metabolism than strong exercise, such as high-speed running. This is consistent with suggestion that light exercise might be effective in clinical treatment for hyperlipidemia, arteriosclerosis or fatty liver.
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PMID:Dependence of lipid-lipoprotein metabolism on exercise intensity in experimental fatty liver rats. 325 7

The apo E locus contributes to determining the variation in plasma cholesterol levels of healthy and diseased populations. It also influences the expression of hyperlipidemia and appears to modulate the susceptibility to atherosclerosis in a complex multifactorial interaction. There is evidence that the presence of apo E2 is protective, whereas that of apo E4 predisposes to coronary artery disease. The burden of proof, however, lies on future, well-designed clinical trials and prospective studies. The study of the biological significance of the apo E polymorphism in humans has emphasized the importance of gene-gene and gene-environment interactions in the pathogenesis of hyperlipidemia and atherosclerosis. The apo E polymorphism involves the coding region of the apo E gene and results in alterations of the gene product which, in turn, either directly or secondarily affect the metabolic fate of the lipoprotein particles. Rapid advances in knowledge over the last decade have provided a metabolic explanation for the observation of the opposite effects of the epsilon 4 and the epsilon 2 alleles on lipoprotein levels. Apo E2 has lower receptor binding affinity which results in delayed clearance of apo E2-bearing lipoprotein particles from plasma. Apo E4 is distributed differently from apo E3 between VLDL and HDL, is degraded more rapidly than apo E3, and may enhance the catabolism of E4-bearing particles, leading to other alterations in lipoprotein metabolism which result in elevated levels of LDL. In view of the significant opposite impacts of the epsilon 4 and the epsilon 2 alleles on plasma LDL cholesterol concentrations, it is evident that determination of the apo E phenotype will become a useful adjunct to the assessment of the cardiovascular risk profile of an individual. In addition, the relationship between the epsilon 2 allele and type III hyperlipoproteinemia provides a valuable model for the study of complex genetic interactions in the pathogenesis of hyperlipidemia. The further study of apo E and its interactions shows great promise for a deeper comprehension of the pathogenesis of atherosclerosis.
Arteriosclerosis
PMID:Apolipoprotein E polymorphism and atherosclerosis. 327 11


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