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)

Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to increased serum concentration of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This disorder is associated with a G to A mutation in exon 26 of the apolipoprotein B (apo B) gene which creates a substitution of glutamine for arginine in the codon for amino acid 3500. We have searched for this mutation in 374 unrelated individuals with hyperlipidaemia from the United Kingdom, and in 371 unrelated individuals with a primary clinical diagnosis of atherosclerosis from the United Kingdom and Scandinavia. Ten individuals, 9 from the U.K. and 1 from Denmark, were identified. The frequency of the mutation was 3% in individuals classified clinically as having familial hypercholesterolaemia (FH) and 3% in individuals with type IIa hyperlipidaemia without FH, and was not found in patients with types IIb and III hyperlipidaemia. The mutation was rare in individuals with a primary clinical diagnosis of atherosclerosis. Plasma lipid levels and clinical characteristics of the ten patients identified in the present study are similar to those reported for heterozygous FH. Thus, in our study, FDB is associated with moderate to severe hypercholesterolaemia, and appears to be a serious disorder causing premature cardiovascular disease. Individuals with this mutation can be identified unambiguously using routine molecular screening techniques.
Atherosclerosis 1990 Jan
PMID:Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases. 231 Apr 29

We examined the relationship between cholesterol synthesis and high affinity low density lipoprotein (LDL) catabolism in freshly isolated mononuclear leukocytes and plasma sterols and apolipoprotein concentrations in three homozygous and one heterozygous subject with sitosterolemia with xanthomatosis and in 12 control subjects. Observations in untreated subjects were compared during therapy with lovastatin or interruption of the enterohepatic circulation of bile acids. Plasma cholesterol, plant sterol, and apolipoprotein B concentrations declined more than 50% in the two homozygous sitosterolemic subjects after ileal bypass surgery. In contrast, plasma cholesterol, plant sterol, and apolipoprotein B concentrations remained constant in a homozygous sitosterolemic subject and declined only 7% in a heterozygous sitosterolemic subject during 20 weeks of lovastatin (40 mg/day) treatment compared to a 28% decrease in similarly treated control subjects. Lovastatin treatment decreased cholesterol synthesis more than 60% but did not increase high affinity catabolism of LDL further in the sitosterolemic cells, compared to a more than 20% rise in control mononuclear leukocytes. Conversely, bile acid malabsorption increased cholesterol synthesis 59%, total hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity 13%, and receptor-mediated LDL degradation 41% in control cells, but did not stimulate cholesterol synthesis or microsomal HMG-CoA reductase activity in sitosterolemic mononuclear leukocytes although receptor-mediated LDL catabolism rose an additional 26%. These results demonstrate a greater than expected decrease in plasma sterols and apolipoprotein B concentrations in sitosterolemic subjects after stimulation of bile acid synthesis because of the inability to up-regulate cholesterol production. We suggest that bile acid-sequestering drugs or ileal exclusion surgery may be more effective treatments to mobilize accumulated sterol deposits and prevent atherosclerosis in this disease.
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PMID:Unexpected failure of bile acid malabsorption to stimulate cholesterol synthesis in sitosterolemia with xanthomatosis. Comparison with lovastatin. 231 63

Modest numbers of blood monocytes become attached at least temporarily to the endothelium of large arteries in normal swine fed low fat, low cholesterol diets. These numbers are increased several fold when the swine are fed a high saturated fat, high cholesterol atherogenic diet (BT). The main objective of this portion of a broader study was to see if the addition of fish oil (30 ml) to a BT diet (BT + FO) could prevent the increase in attached monocytes induced over arterial endothelium in BT fed swine. Six BT, 6 BT + FO and 5 control mash (MA) swine fed the respective diets for 4 months before killing were available for the current study. Other aspects of this experiment have been presented previously which in brief are that BT + FO resulted in retardation of atherosclerotic lesion development and a shift in lipoprotein components from predominantly apolipoprotein B,E containing with the BT diet to predominantly apo B only with BT + FO. There was a significant positive correlation between lesion development and apo B,E lipoproteins. In the current study we determined by scanning electron microscopy on the first portion of the left anterior descending coronary artery after perfusion fixation under pressure the number of monocytes per mm2 attached over or not over visible lesions. We also determined monocyte percentages in the circulating blood and analyzed the correlation of the numbers of attached monocytes and blood monocyte percentages with various lipoprotein components reported previously.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1990 Apr
PMID:Dietary fish oil added to a hyperlipidemic diet for swine results in reduction in the excessive number of monocytes attached to arterial endothelium. 235 Mar 71

Several recent reports have examined whether there is a correlation between the presence of some minor alleles of the highly polymorphic apolipoprotein B gene and atherosclerosis and premature heart disease. The present study extends this investigation. A high-resolution method was used to study the allele frequencies of a hypervariable minisatellite region close to the apolipoprotein B gene in 110 patients with severe coronary disease and in 117 normal controls. Alleles containing 38, 44, 46, or 48 hypervariable elements showed an association with coronary heart disease. These alleles were also associated with elevated serum levels of total cholesterol and apolipoprotein B among patients and with elevated serum levels of total triglycerides among controls. The hypervariable region showed strong linkage disequilibrium with a polymorphic EcoRI site in exon 29 and was in linkage equilibrium with a polymorphic MspI site in exon 26. Two patients carried a base change at codon 3500 that results in an arginine-to-glutamine substitution; the base change was linked in both instances to the allele with 48 hypervariable elements.
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PMID:Hypervariability in a minisatellite 3' of the apolipoprotein B gene in patients with coronary heart disease compared with normal controls. 235 70

When bezafibrate therapy was interrupted in patients who had been on continuous treatment for hyperlipoproteinemia for 4-10 years, there were significant increases in the serum cholesterol, triglyceride and apolipoprotein B concentrations corresponding to an increase of the very low density lipoprotein (VLDL) levels by approximately 50%. This increase of VLDL was accompanied by reduced levels of the post-heparin lipoprotein lipase activity (LPLA) (P = 0.07) and hepatic lipase (P = 0.05) activity with a significant reduction of the skeletal muscle LPLA (P less than 0.05), but not the adipose tissue LPLA, and a retarded removal of an i v injected fat emulsion (P less than 0.01). There were no significant changes of the low or high density lipoprotein cholesterol or the apolipoprotein A-I or A-II concentrations. Three months after bezafibrate treatment the content of linoleic and gammalinoleic acid in the plasma cholesterol ester had increased significantly, while the palmitoleic and oleic acids were reduced in spite of unchanged dietary treatment. Taken together, the data indicate that a lipid-lowering effect of bezafibrate, particularly on the VLDL lipids, is maintained throughout long treatment periods. One mechanism for the reduced level of the triglyceride-rich lipoproteins is an increased activity of the lipoprotein-lipase activity in the skeletal muscle, which decreased when the treatment was interrupted. The significance of the changes of the plasma lipid fatty acid spectrum during bezafibrate treatment remains unclear.
Atherosclerosis 1990 May
PMID:Interruption of long-term lipid-lowering treatment with bezafibrate in hypertriglyceridaemic patients. Effects on lipoprotein composition, lipase activities and the plasma lipid fatty acid spectrum. 236 Sep 15

The relationships between plasma lecithin:cholesterol acyltransferase (LCAT) mass concentrations and lipids, apolipoprotein, and lipoprotein subfraction concentrations were studied in men assigned at random to a one-year exercise program (n = 48) and to a sedentary control condition (n = 31). Exercise training did not significantly affect mean concentrations of LCAT-mass. Moreover changes in LCAT within the exercise group were unrelated to distance run and weight loss. The baseline data and the one-year change data showed consistent positive correlations between LCAT concentrations and total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, and apolipoprotein B concentrations, and consistently weak correlations between LCAT concentrations and high density lipoprotein (HDL)-cholesterol, HDL2, and apolipoprotein A-I concentrations. The strong correlation between LCAT and total cholesterol may account for LCAT's relationships with lipoprotein subfractions, apolipoprotein B and other lipoprotein cholesterol concentrations.
Atherosclerosis 1990 May
PMID:Associations of lecithin: cholesterol acyltransferase (LCAT) mass concentrations with exercise, weight loss, and plasma lipoprotein subfraction concentrations in men. 236 Sep 20

Familial defective apolipoprotein B-100 is a genetic disorder which is associated with elevated plasma LDL levels. It appears to result from a G----A mutation at nucleotide 10,708 in exon 26 of the apolipoprotein B-100 gene leading to a substitution of glutamine for arginine at amino acid residue 3500. We explored the possible role of this point mutation as a cause of elevated plasma cholesterol among the Finns, a genetically isolated population in which both hypercholesterolemia and coronary heart disease are common: 552 hyperlipidemic patients from Western and Southern Finland were screened either by assaying patient sera with monoclonal antibody MB47 or by amplifying the region of the apo B gene containing the nucleotide 10,708 followed by hybridization of the amplified DNA with allele-specific oligonucleotide probes. Not a single individual with this particular mutation could be found. We conclude that familial defective apo B-100 is not a common cause of elevated plasma cholesterol in this population.
Atherosclerosis 1990 Jun
PMID:Absence of familial defective apolipoprotein B-100 in Finnish patients with elevated serum cholesterol. 237 82

One hundred and fifty-four male and 69 female Chinese patients, aged between 40 and 60 years, who had suffered myocardial infarction (MI) were investigated and compared with 216 men and 219 women who had no history or ECG evidence of coronary heart disease. The male MI patients had significantly raised levels of triglycerides (160 mg/dl), cholesterol (194 mg/dl), VLDL-CH (31 mg/dl), apolipoprotein B (122 mg/dl) and apolipoprotein E (4.7 mg/dl) and a lower apolipoprotein A-I level (126 mg/dl) than the control group (triglycerides 131, cholesterol 179, VLDL-CH 26, apo B 102, apo E4.2, and apo A-I 138 mg/dl). The women with MI also had higher values for the atherogenic lipids than the control group (triglycerides 175 vs. 134 mg/dl, cholesterol 218 vs. 186 mg/dl, LDL-CH 128 vs. 104 mg/dl, VLDL-CH 32 vs. 26 mg/dl, apo B 121 vs. 103 mg/dl and apo E 5.4 vs. 4.3 mg/dl), as well as lowered apolipoprotein A-I (128 vs. 144 mg/dl). The Lp(a) levels (men and women considered together) were significantly higher for the MI patients (34.3 mg/dl vs. 26.2 mg/dl). Anti-atherogenic lipoproteins such as HDL-cholesterol, HDL2-CH, HDL3-CH, phospholipids and apolipoprotein A-II, C-II and C-III showed no difference between the groups.
Atherosclerosis 1990 Jun
PMID:Lipids, lipoproteins, apolipoproteins, and other risk factors in Chinese men and women with and without myocardial infarction. 237 89

A 14-yr-old Turkish girl presented with serum cholesterol levels of 15-20 mmol/l, skin and tendon xanthomata, and anginal attacks. A coronary angiography demonstrated severe coronary atherosclerosis including a 70% stenosis at the origin of the left coronary artery. The clinical diagnosis, homozygous familial hypercholesterolaemia, was confirmed by: (1) investigation of the family revealing hypercholesterolaemia in both her parents and siblings; (2) fibroblast association studies, in which the specific association of low density lipoprotein (LDL) was 35% of normal; and (3) LDL turnover study, in which the fractional catabolic rate of LDL was decreased to 0.213 pools/day. Treatment with cholestyramine or simvastatin had little effect on serum cholesterol levels. After coronary artery bypass grafting, the patient was treated with selective LDL apheresis using columns containing dextran-sulphate bound to cellulose. These columns bind apolipoprotein B containing lipoproteins but not high density lipoproteins. After 2 yr of therapy, the level of serum cholesterol has declined by 56%. Skin xanthomata have disappeared and there is no recurrence of angina pectoris. On repeated coronary angiography, two of the three bypasses are patent and there is no progression of atherosclerotic lesions. We conclude that LDL apheresis is an efficient procedure to lower serum cholesterol in patients who do not respond to pharmacological treatment of hypercholesterolaemia.
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PMID:Homozygous familial hypercholesterolaemia: metabolic studies and treatment with LDL apheresis. 239 95

A within-group risk factor analysis was conducted to predict angiographic change in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled trial of colestipol plus niacin therapy in men with previous coronary bypass surgery. Global angiographic change, including both native coronary arteries and bypass grafts after 2 treatment years, was the end point. Risk factors included on-trial clinical measures, plasma lipids, lipoproteins, and apolipoproteins. Univariate analysis indicated that risk factors previously observed by others in epidemiologic investigation of ischemic heart disease--total cholesterol, LDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein B, and diastolic blood pressure--had significant effects in the placebo-treated group. Univariate analysis indicated significant effects of apolipoprotein C-III in drug- and placebo-treated groups. Multivariate analysis indicated the predominant risk factor predicting the probability of global coronary progression was non-HDL cholesterol in placebo-treated subjects and the content of apolipoprotein C-III in high density lipoproteins of drug-treated subjects. Both drug- and placebo-treated group findings point to an important role for triglyceride-rich lipoproteins in progression and regression of human atherosclerosis.
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PMID:Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts. Lipid and nonlipid factors. 229 71


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