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)

High-density lipoprotein (HDL) cholesterol levels have an inverse relationship with the frequency of coronary and cerebrovascular disease. Most commonly HDL deficiency is environmentally modulated. Familial hypoalphalipoproteinemia (FHA) is a genetically determined HDL deficiency disease, in all likelihood transmitted as an autosomal dominant trait and associated with premature atherosclerosis. Apolipoprotein AI (apo AI) is the major apoprotein in the HDL particle, and defects in this protein have been suggested as the cause of FHA. We have identified a large family of Spanish descent with FHA and performed genetic linkage analysis using restriction fragment length polymorphisms in the Apo AI-CIII-AIV gene cluster to test this hypothesis. Results in this family formally exclude the apo AI-CIII-AIV gene cluster as the site for the mutation underlying FHA.
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PMID:The gene causing familial hypoalphalipoproteinemia is not caused by a defect in the apo AI-CIII-AIV gene cluster in a Spanish family. 196 39

The familial hypoalphalipoproteinemias are a heterogeneous group of rare lipoprotein disorders characterized by extremely low levels of plasma high density lipoproteins (HDL) and, in most cases, autosomal recessive inheritance. Most of these conditions present distinctive and diagnostic clinical and laboratory abnormalities. In spite of the marked reductions in HDL, however, many of these conditions are not associated with premature atherosclerosis. This is true of Tangier disease, Fish Eye disease, lecithin: cholesterol acyltransferase deficiency, and of some variants of apo Al. Another condition, defined as a primary and familial decrease in HDL-cholesterol levels in the absence of other lipoprotein abnormalities. that is associated with premature atherosclerosis was originally called Familial Hypoalphalipoproteinemia but is better referred as to Familial Isolated Hypoalphalipoproteinemia. At present, the prevalence, inheritance, and the underlying defect(s) in this disorder are unknown. Decreased or absent synthesis of apo A-I due to a gene defect is the cause of apo A-I/C-III and apo A-I/C-III/A-IV deficiency. However, the etiology of the low levels of HDL is unclear for most of the remaining familial hypoalphalipoproteinemias. Increased catabolism, decreased synthesis and altered equilibration of HDL between intra- and extravascular spaces have all been suggested as underlying causes of low plasma HDL. Whatever their causes, these disorders are associated with altered HDL composition and altered equilibration of cholesterol amongst the various lipoprotein classes. The absence of consistent correlation with premature atherosclerosis in many of these conditions suggests that the protective effect of HDL may reside in a quantitatively small, but metabolically active subfraction of HDL particles.
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PMID:Familial hypoalphalipoproteinemias. 211 26

In 25 patients with primary dyslipoproteinemias and severe premature atherosclerosis, during an average combined Lopid-Mevacor treatment span of 12.5 months per patient, our specific aim was to assess safety and efficacy of open-label therapy with diet, gemfibrozil (Lopid), and lovastatin (Mevacor). Because targeted lipid values were not reached on diet alone (low-density lipoprotein cholesterol [LDLC] less than 120 mg/dl, high-density lipoprotein cholesterol [HDLC] greater than 35 mg/dl or total cholesterol [TC]/HDLC less than 4.5), the patients received Lopid, 1.2 gm/day as their initial lipid-lowering drug. Because targeted lipid levels were not reached with Lopid treatment alone after 3 or more months, Mevacor was added, with 17 subjects receiving 20 mg/day, five receiving 40 mg, two receiving 60 mg, and one receiving 80 mg. Outpatient visits were repeated during combined therapy every 6 to 8 weeks, with an average of 6.4 visits per subject, 162 measurements of fasting lipids and liver function tests, and 127 measurements of creatine phosphokinase (CPK). By selection, all patients had normal liver function (gamma-glutamyltransferase, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) levels) and normal CPK levels at baseline. No gamma-glutamyltransferase levels were high during combined therapy. Of the 162 liver function test measurements, five (3.1%) SGOT levels and three (1.9%) SGPT levels were high. Of 127 CPK measurements, three (2.4%) were high; one subject had a high CPK measurement, and one subject had two high measurements for CPK. No symptomatic myositis or myalgias developed in the subjects; none had palpable skeletal muscle tenderness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Safety and efficacy of combined gemfibrozil-lovastatin therapy for primary dyslipoproteinemias. 234 62

The levels of plasminogen activator inhibitor (PAI), protein C (pC), total cholesterol (TC), high and low density lipoprotein cholesterols (HDLC and LDLC), apolipoproteins A1 (apoA1) and B (apoB) were measured in 45 patients with coronary heart disease angiographically documented and 10 healthy subjects without coronary heart disease and coronary atherosclerosis as evidenced by coronary angiography and provocative tests. Twenty three patients had primary angina (PA) with a duration of less than 3 months, twenty two patients presented with chronic coronary heart disease (CCHD) with a duration of more than 4 months. In general, a negative correlation between PAI and HDLC levels in the patients under study (r = -0.413; p = 0.02), it was higher in PA (r = -0.687; p = 0.02), but disappeared in CCHD (r = 0.027). The content of PAI correlated with the cholesterol index (r = 0.654; p less than 0.001 in the whole group), more greatly in PA (r = 0.865; p = 0.001) than in CCHD (r = 0.506, NS). There was a good correlation between the levels of pC and apoB in the whole group (r = 0.606; p less than 0.001) and in PA (r = 0.662; p = 0.001), but not in CCHD (r = 0.288, NS). The content of pC also correlated with a apoB/apoA1 ratio (r = 0.445; p = 0.002 in the whole group of patients). This correlation was significantly positive in PA (r = 0.455; p = 0.044), but not in CCHD (r = 0.022). Thus, higher levels of PAI coincided with atherogenic changes in those of HDLC, and an increase in the content of pC was in agreement with that of apoB. The interrelationships are particularly typical of early stages of CHD.
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PMID:[Plasminogen activator inhibitor and protein C: their relation to plasma lipids and lipo- and apoproteins in ischemic heart disease of different duration]. 239 63

Anaesthetized mongrel dogs were subjected to occlusion of a coronary artery. The resulting myocardial infarction was observed for three hours. One hour after occlusion, infusion of the stable prostacyclin analogue iloprost or saline was started. In the control group myocardial infarction was associated with an increase of the ratio TXB2/6-keto-PGF1a which was abolished by iloprost treatment. After occlusion in the control group, the atherosclerosis index (TC-HDLC): HDLC was increased, but in the iloprost-treated group it was significantly decreased. The results of this study suggest that the administration of iloprost is able to prevent changes in eicosanoid metabolism and lipoprotein pattern after coronary artery occlusion in dogs.
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PMID:Influence of iloprost on eicosanoid generation and lipid levels in experimental myocardial ischemia in dogs. 246 84

We report here a peculiar case with premature corneal opacity and extremely high levels of HDL cholesterol in serum. The patient is a 54-year-old man who was first noticed to have marked corneal opacities at age 19. His serum HDL cholesterol level was elevated to the level of 135-160 mg/dl, while total serum cholesterol and triglyceride concentrations were 254 mg/dl and 56 mg/dl, respectively. Serum apoprotein A-I and E levels analyzed by single radial immunodiffusion method were elevated in the case. Serum lipoprotein fractions isolated by preparative ultracentrifugation revealed that increased levels of HDL cholesterol were accounted for solely by the HDL2 fraction. HDL2 of the patient contained relatively higher amounts of apoprotein E than normal control HDL2. Elution profiles of lipoproteins in high performance liquid chromatography revealed that HDL2 particles from the patient were larger in size than those from normal controls. These characteristics of HDL are in part similar to those of HDLC which appears in experimental animals after cholesterol feeding. Such abnormalities in HDL2 fractions associated with premature corneal opacity have not been reported so far and appear to constitute a new disease entity.
Atherosclerosis 1984 Nov
PMID:Marked hyper-HDL2-cholesterolemia associated with premature corneal opacity. A case report. 651 75

The incidence of fasting HLP in 326 diabetics was 68.4 percent. The common types of HLP were type IV, IIb, IIa and III respectively. There was one case of type V. HDLC was decreased in all three groups of diabetics together with elevated ratio of TC to HDLC comparing with the controls of similar age and sex VLDL and TG were significantly elevated in NIDDM aged 60 and over comparing with IDDM but not significantly different from NIDDM aged below 60. The early detection and treatment of HLP along with optimum control of blood glucose are of utmost importance to prevent further complications caused by atherosclerosis.
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PMID:Lipid disorders in Thai diabetics. 668 May 38

Previous studies from this laboratory have determined that diets containing the usual amounts of fat to which are added 750-1500 mg/day cholesterol elevate the plasma cholesterol concentration by variable amounts, depending upon the ratio of polyunsaturated to saturated fatty acids (P/S ratio) of the diet. Diets with P/S ratios of 0.25-0.4 are accompanied by elevations of low density lipoprotein (LDL) cholesterol, whereas diets with a P/S ratio of 2.5 produce no significant changes in cholesterol levels. On the low P/S ratio diets, the structure, composition, and interaction with cultured fibroblasts of LDL are not significantly changed. Plasma high density lipoprotein (HDL) cholesterol levels remain constant, but HDL2 increase relative to HDL3. In the present study, not only dietary cholesterol but also total dietary fat was altered. Six normal young men were fed a basal diet consisting of 18% protein, 51% carbohydrate, and 30% fat, containing 250 mg/day cholesterol. After 2 weeks, an experimental diet consisting of 18% protein, 42% carbohydrate, and 39% fat, containing 1760 mg/day cholesterol, was fed for 4 weeks. The P/S ratios of both diets were about 0.4. Plasma samples were taken twice during each dietary period from 12- to 14-h-fasted subjects and analyzed for their contents of lipoprotein lipids. Plasma levels of LDL and HDL cholesterol increased by 30 and 13 mg/dl, respectively; total and very low density lipoprotein (VLDL) triglyceride concentrations were unaltered. The plasma concentrations of apoproteins (apo) B, E. and A-I, but not A-II, were elevated. Plasma samples also were studied by zonal ultracentrifugation, gel permeation column chromatography, and Pevikon electrophoresis. Although on zonal ultracentrifugation the total concentrations of LDL were increased, the flotation properties and chemical compositions of LDL were not changed. By contrast, HDL2 and HDL3L concentrations increased, and HDL2 became enriched with cholesteryl esters. On gel permeation chromatography, with the subjects on the basal diet, plasma cholesterol eluted in two peaks, corresponding to LDL and HDL. The sizes of the peaks increased on the experimental diet. ApoE eluted in two peaks: one at the leading edge of LDL (corresponding to VLDL or IDL) and the other in the area between LDL and HDL, corresponding to HDLC. On the experimental diet, the apoE peak between LDL and HDL increased. On Pevikon electrophoresis apoE migrated between the LDL and HDL bands. This apoE peak was increased on the experimental diet. These findings suggest that increasing the concentrations of both dietary cholesterol and total fat can increase the levels of plasma LDL, HDL2, and HDLC in fasting normal subjects. Thus, the concentrations of some putatively atherogenic as well as antiatherogenic lipoproteins increased in plasma, and the apparent paradox between the epidemiological and metabolic behaviors of some lipoproteins remains. Clearly, more work is needed to resolve the roles of various lipoproteins in plasma in atherosclerosis.
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PMID:Increases in dietary cholesterol and fat raise levels of apoprotein E-containing lipoproteins in the plasma of man. 684 53

High levels of low density lipoprotein (LDL) and its apolipoprotein B (apoB) are risk factors for atherosclerosis and myocardial infarction (MI). There is rich genetic polymorphism in apoB, first detected as the Ag allotypes of LDL, but today mostly examined at the DNA level. Genes contribute to the population variation in LDL and apoB levels and alleles in polymorphisms at the apoB locus are candidate genes with respect to control of lipid levels and susceptibility to atherosclerosis and MI. The XbaI polymorphism at the apoB locus, which involves the third base of threonin codon 2488 (ACC-->ACT) without changing the amino acid sequence was examined in a case-control study comprising 238 survivors of myocardial infarction (MI) and 621 controls. In univariate analysis, frequencies of genotypes in this polymorphism were not statistically different between patients and controls of either sex. However, in multivariate logistic regression analysis, the odds ratio X-X- homozygotes (homozygotes for absence of restriction site) for having MI compared to the pooled group of heterozygotes and X+X+homozygotes (homozygotes for presence of restriction site) was 2.16 (p = 0.007), after adjustments for age, sex, and levels of apoB, high density lipoprotein (HDL) cholesterol (HDLC) and Lp(a) lipoprotein. It appeared that heterozygotes do not have increased risk, compared to the X+X+ homozygotes. Stratification according to low or high levels of apoB, HDLC and Lp(a) lipoprotein, showed that the X-X- genotype was more common in patients than controls, in all subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:XbaI polymorphism in DNA at the apolipoprotein B locus is associated with myocardial infarction (MI). 790 11

A 60-year-old homozygous patient with familial high density lipoprotein deficiency (Tangier disease) was examined by coronary angiography and intravascular ultrasound because of typical angina pectoris. We found a normal left ventricular function, moderately diffuse coronary sclerosis without stenosis, and no critical stenosis of peripheral arteries. Intravascular ultrasound revealed normal thickness and the three-layer appearance of the arterial intima, media, and adventitia within the peripheral arteries, and showed a single, discrete arteriosclerotic lesion in one iliac artery segment. The lack of severe atherosclerosis was remarkable insofar as massive foam cell formation in reticuloendothelial tissues and the virtually complete absence of circulating HDL is characteristic of Tangier disease and had been previously demonstrated in this patient.
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PMID:[Coronary angiography and intravascular ultrasound examination of a 60-year-old patient with familial HDL deficiency (Tangier disease)]. 805 48


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