Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well established that elevated plasma levels of low-density lipoprotein (LDL) particles are a risk factor for ischaemic heart disease with the distribution in LDL levels seen in the general population being the result of interaction between environmental factors, such as dietary fat intake, and genetic variation that is present in different individuals. One of the candidate genes where such variation is likely to occur, is the gene coding for apolipoprotein B (apo B). Many studies have reported an association between a common polymorphism of the apo B gene, detected using the restriction enzyme XbaI, and differences in plasma lipid levels, explaining 3-5% of the variance in LDL-cholesterol levels in samples representative of the healthy population. It has been proposed that the mechanism of this association is due to functional amino acid changes within the apo B protein, that affect LDL catabolism by altering binding affinity to the LDL-receptor. Several amino acid substitutions in the apo B gene have now been characterized, and these form the basis of the different epitopes that create the Ag marker system. Previous studies have reported that the Ag(x) epitope is associated with lower plasma lipid levels, and until recently the molecular basis for this association has been unclear. We have determined that the Ag(x) epitope is associated with both a Pro-Leu2712, and Asn-Ser4311 substitution, with the Leu-Ser allele being associated with significantly lower levels of plasma lipids in a sample of healthy individuals from Sweden.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:DNA polymorphism studies. Approaches to elucidating multifactorial ischaemic heart disease: the apo B gene as an example. 138 65

The authors investigated selected indicators of the lipid metabolism in 31 children with insulin-dependent diabetes for a period of 3 to 14 years. They divided the patients into two groups those with a glycosylated haemoglobin below or above 9 mumol/1 g haemoglobin. They compared the assembled results of the two groups and also with the results obtained in a control group. The total cholesterol was in both diabetic groups higher than in healthy subjects and was higher than the value which is considered from the aspect of the genesis and development of atherosclerosis as a risk value. Children with poorly compensated diabetes, i. e. with a glycosylated Hb level above 9 mumol had a higher cholesterol level as compared with well compensated diabetic children. The pre-beta fraction of lipoprotein increased in both groups of patients, however, more in those where the disease was not well compensated. There was a parallel decrease of the alpha fraction and the lipoprotein profile had a markedly atherogenic character. The apolipoprotein B concentration was in patients with well compensated diabetes lower, as compared with controls but in patients with poorly compensated diabetes after 4-5 years treatment is was significantly higher. Poor compensation of diabetes led after 4-5 years duration to a significant rise of the serum triglyceride level. As the blood lipid levels are influenced in a significantly way by diet, compensation of the disease and a low-fat diet are essential with regard to the results assembled in this investigation for prevention of ischaemic heart disease in diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Variations in lipid metabolism in long-term monitoring of children treated for diabetes mellitus]. 139 53

It is concluded on the basis of literature data, that apolipoprotein B-100 is the most high-molecular, hydrophobic, and positive charged protein compared to the other apoproteins of the plasma lipoproteins. Low density lipoproteins of healthy subjects, mainly containing apo B-100, have little heterogeneity on both charge and isoelectric point, in spite of heterogeneity on sizes and apolipoprotein composition. The reason of formation of subfraction with elevated negative charge is the damage with the free radicals and/or aldehydes. The reason of formation of more cationized subfraction is unclear. LDL charge changes are noted in some diseases and syndromes (ischemic heart diseases, familial hyper-alpha-lipoproteinemia, Tangier disease, X-bound ichthyosis and, possibly, others). Some IHD patients treatment with antioxidants leads to the disappearance of negative charged LDL subfraction, that shows participation of peroxidation products in their formation. Electrical characteristics of LDL of tissue fluids and of aorta wall differ essentially from those of the same class plasma lipoproteins. Lipid peroxidation and influences of several enzymes play the main role in these differences.
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PMID:The charge and atherogenicity of low density lipoproteins. 144 71

We measured serum lipoprotein(a) [Lp (a)] concentrations in 50 uremic patients treated on continuous ambulatory peritoneal dialysis (CAPD) and compared them with those in 29 uremic patients on hemodialysis (HD) and those in 62 normal controls. The median values were 47.9 mg/dl in CAPD patients, 25.2 mg/dl in HD patients, and 11.7 mg/dl in controls, respectively. These differences were statistically significant when assessed by Kruskal-Wallis test (p < 0.0001). Thirty-five out of 50 patients on CAPD (70%) and 12 out of 29 patients on HD (41%) had Lp(a) concentrations above 30 mg/dl, whereas these high values were observed in only 15% of normal controls. This difference in prevalence of high Lp(a) was also significant by 2 x 3 chi-square test (p < 0.01). There was a significant positive correlation between Lp(a) and apolipoprotein B (r = 0.517, p < 0.0001). In CAPD patients, 9 with ischemic heart disease had a significantly higher median Lp(a) than those without it (67.4 vs 40.9 mg/dl, p < 0.01 by Mann-Whitney U-test). These results suggest that high levels of serum Lp(a) might contribute to an increased risk for ischemic heart disease in CAPD patients, and that there may be a relationship between Lp(a) and apolipoprotein B metabolism in CAPD patients.
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PMID:High serum lipoprotein(a) concentrations in uremic patients treated with continuous ambulatory peritoneal dialysis. 145 40

Automated methods for the determination of apolipoprotein B and apolipoprotein A-I were developed, tested, and applied in screening programs of large populations to improve information about the composition and degree of hyperlipoproteinemia. Apolipoproteins B and A-I, total cholesterol, and triglyceride levels were measured in 25,659 males and 18,144 females between 20 and 79 years of age, the majority subjectively healthy. The immunoturbidimetric methods used for apolipoproteins B and A-I were shown to be stable over time, and the errors of the methods were below 7%. Apolipoprotein B correlated with total cholesterol (r = 0.86, P less than 0.001) for each age decile group and for both sexes (r = 0.82-0.87, P less than 0.001). For a subsample comparable to the large population, apolipoprotein B correlated with cholesterol in low density (i.e., the atherogenic particle), r = 0.89, P less than 0.001. The mean values for apolipoprotein B increased with age for both sexes, with much higher levels in males than in females under 50 years of age. Apolipoprotein A-I was lower in males than in females in all age-groups. At all cholesterol levels males had higher apolipoprotein B, and at the same triglyceride level, also lower apolipoprotein A-I and hence a higher B/A-I ratio than females. Using apolipoprotein B and A-I (high-density lipoprotein cholesterol) particles and adopting Swedish consensus criteria for the diagnosis of risk of ischemic heart disease, examples are given showing that many individuals, especially females, with high or borderline total serum cholesterol can be excluded from further investigation/treatment for hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoprotein B and A-I in relation to serum cholesterol and triglycerides in 43,000 Swedish males and females. 159 76

The aim of the study was to examine the relationships of obesity, lipids and apolipoproteins with the risk for subsequent ischaemic heart disease in middle-aged women, using a case-control study nested within a cohort study. A total of 3634 women aged 26-88 were recruited in Guernsey between 1977 and 1985 and followed until June 1986 by abstraction of their general practitioners' records. Fifty-one cases of incident ischaemic heart disease (11 myocardial infarction, 40 angina) were identified. For each case up to 4 controls were selected, matched for age and date at recruitment. Odds ratios for the development of ischaemic heart disease in the middle and upper thirds of the distribution for each variable in the controls, relative to the lowest third (and two-sided P-values for linear trends), were: 3.0, 2.6 (0.015) for Quetelet's index; 3.3, 5.1 (0.003) for total cholesterol; 0.5, 0.6 (0.102) for apolipoprotein A-I; 1.8, 2.4 (0.015) for apolipoprotein B; 1.3, 2.1 (0.155) for apolipoprotein(a). The increased risks associated with increased Quetelet's index and total cholesterol were independent of each other and these variables were more strongly related to myocardial infarction than to angina. The relationships of risk with serum cotinine, fatty acids, dehydroepiandrosterone sulphate and sex hormone binding globulin were weak and did not approach statistical significance.
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PMID:A prospective study of obesity, lipids, apolipoproteins and ischaemic heart disease in women. 163 46

We have examined DNA polymorphisms associated with the apolipoprotein B gene in 95 Sri Lankan males with ischaemic heart disease and 95 matched controls. For polymorphisms detected using the XbaI or MspI enzymes the allele frequency in Sri Lankans contrasted markedly from that in Caucasians. Overall, there was no significant association of any allele studied with coronary disease cases in this sample. There was, however, a significant difference observed between the XbaI allele frequency in normotriglyceridaemic or normocholesterolaemic CHD cases compared with the allele frequency in the controls.
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PMID:Restriction fragment length polymorphisms in the Apo B gene in relation to coronary heart disease in a southern Asian population. 167 37

The authors administered lovastatin (Mevacor, MSD) to 18 patients with primary hyperlipoproteinaemia (familial and non-familial) with a lipoprotein pattern type IIa and IIb. During treatment a marked reduction of atherogenic indicators of the lipid metabolism occurred, i.e. a decline of total cholesterol (-28.6%), LDL-cholesterol -39%), apolipoprotein B (-18.6%), the index of total cholesterol/HDL-cholesterol (-44.6%) and the index LDL-cholesterol/HDL-cholesterol (-48.2%). At the same time a favourable effect on indicators of the lipid metabolism to which a protective action is ascribed was recorded: a rise of HDL-cholesterol (+13.6%) and apolipoprotein AI (+13%) and AII (+13%). An excellent effect was observed also in four heterozygotes with familial hypercholesterolaemia which is usually rather resistant to other types of hypolipidaemic treatment. The drug was very well tolerated and subjective side-effects of treatment were minimal. Despite the fact that a number of laboratory indicators was followed up, the authors did not observe any undesirable side-effects, only a transient and marginal rise of ALT in one patient. Lovastatin is, due to its potent hypolipidaemic effect, a new hope in the treatment of hypercholesterolaemia. Its usefulness in the prevention of ischaemic heart disease, as well as its safety during prolonged administration are tested at present in long-term investigations.
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PMID:[Personal experience with lovastatin, a HMG-CoA reductase inhibitor (Mevacor, MSD) in the treatment of hypercholesterolemia]. 184 44

Non-insulin-dependent diabetic (NIDDM) subjects exhibit abnormalities in their plasma lipid and lipoprotein profiles that increase the risk of ischemic heart disease. This study was designed to examine the metabolic behavior of very-low-density (VLDL), intermediate-density (IDL), and low-density (LDL) lipoproteins in NIDDM patients before treatment and after 4 wk of insulin therapy. Basal turnover studies of 131I-labeled VLDL1 (svedberg units [Sf] 60-400) and 131I-labeled VLDL2 (Sf 20-60) apolipoprotein B (apoB) were conducted in a group of seven NIDDM patients who had been off oral therapy for 1 wk. The subjects exhibited higher than normal transport rates for VLDL1 and a diminished input of apoB into the VLDL2 density range. These observations are concordant with the hypothesis that NIDDM patients overproduce VLDL triglyceride but not apoB. VLDL1 and VLDL2 were converted to IDL and ultimately to LDL at approximately normal rates, although the delipidation pathway by which apoB-containing particles were processed exhibited different properties from that seen in control subjects. Insulin therapy reduced plasma triglyceride by 38%, and this was associated with a 41% fall in VLDL1 mass (P less than 0.01). VLDL2 was less affected (19% reduction, P less than 0.05), IDL was unchanged, and LDL fell 17% (P less than 0.05). Repeat metabolic studies revealed that the major effects of insulin were to reduce VLDL1-apoB transport (from 811 to 488 mg/day) and increase the direct input of VLDL2 into the plasma (from 182 to 533 mg/day, P less than 0.05). These alterations in VLDL production led to normalization of apoB kinetics in IDL and LDL. The fractional catabolic rate of LDL increased 19% (P less than 0.05), whereas direct input into this fraction, which had been high before treatment, was reduced. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase levels were unaffected by insulin, although the hormone did increase LPL in adipose tissue. This lack of effect on lipase activities correlated well with the observation that the rates of catabolism of apoB in VLDL1, VLDL2, and IDL were not significantly affected by insulin therapy.
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PMID:Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM. 220 Jul 27

The incidence of serum antibodies to human low-density lipoprotein, to oxidized low-density lipoprotein, and to ceroid extracted from human atheroma was assessed in 100 subjects using an adaptation of the enzyme-linked immunosorbent assay technique. Patients with chronic periaortitis, subclinical chronic periaortitis, and ischemic heart disease, and "elderly control" individuals were compared with young, healthy adults. Provided that precautions were taken to prevent oxidation of the low-density lipoprotein during the assay, antibodies were not found to native human low-density lipoprotein. Antibodies to oxidized low-density lipoprotein or ceroid, usually both, were detected in all 20 patients with clinical chronic periaortitis, in 17 of 20 patients with subclinical chronic periaortitis, in 12 of 20 patients with ischemic heart disease, and in 10 of 20 elderly control subjects. Binding inhibition studies showed cross-reactions between oxidized low-density lipoprotein and ceroid. Western blotting after sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that in some patients with clinical chronic periaortitis, these antibodies were directed against breakdown products of apolipoprotein B that resulted from oxidation of low-density lipoprotein. Antibodies to oxidized low-density lipoprotein or ceroid were not detected in healthy young adults. These findings show that chronic periaortitis is accompanied by autoallergy to ceroid, which is probably at least partly composed of low-density lipoprotein oxidized within the human atherosclerotic plaque, and that a number of middle-aged and elderly people without chronic periaortitis also have such antibodies.
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PMID:Serum antibodies to oxidized low-density lipoprotein and ceroid in chronic periaortitis. 232 97


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