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)

Recent pharmacological studies confirmed the role of hypercholesterolemia in the pathogenesis of coronary atherosclerosis. A 10% reduction in cholesterol levels can reduce the risk of coronary heart disease by 15%. However many hypercholesterolemic patients often suffer from arterial hypertension and drugs such as thiazide diuretics cause an imbalance in lipid metabolism. The efficacy and the tolerability of simvastatin (a inhibitor of HGM-CoA reductase) with that of gemfibrozil (a fibric acid derivative, which can reduce the VLDL level) were compared in a placebo-controlled study in 2 groups of patients with primary hypercholesterolemia and mild-to-moderate essential hypertension treated with hydrochlorothiazide. After 10 weeks standard hypolipidemic diet and hydrochlorothiazide (25 mg od) therapy, 30 patients whose cholesterol levels were still greater than or equal to 250 mg/100 ml and whose diastolic blood pressure was less than 95 mmHg were randomized to one of the following treatments: simvastatin, 20 mg od, gemfibrozil, 600 mg bid or placebo, while continuing dietetic and diuretic treatment. After 24 weeks treatment, simvastatin induced a 37% reduction in cholesterol plasma levels, a 9% increase of HDL and a 16% reduction of LDL. APO-A1 showed a 4% increase, while APO-B showed a 3% reduction. Gemfibrozil induced a 20% reduction in plasma triglycerides and a 13% decrease in plasma cholesterol, with a significant 19% increase in HDL and a 11% reduction in LDL. No significant variations in any of the lipid parameters monitored were observed in the placebo group. Treatment with simvastatin or gemfibrozil in hypertensive patients in hydrochlorothiazide monotherapy can reduce total cholesterol and LDL-cholesterol plasma levels, while significantly increasing HDL plasma levels compared to placebo. Simvastatin, however, resulted more efficient than gemfibrozil on total cholesterol or cholesterol fractions.
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PMID:[Simvastatin versus gemfibrozil in the treatment of primary hypercholesterolemia in hypertensive patients treated with hydrochlorothiazide]. 224 35

The effects of the beta-blocker tertatolol on plasma lipids and lipoproteins were studied in two groups of 10 normolipidemic (group I) and 10 hyperlipidemic (group II) hypertensive patients, for a period of 3 months. The efficacy of tertatolol was confirmed by a reduction in heart rate (HR), and in systolic (SBP) and diastolic (DBP) blood pressure, in the supine position and after 1 min in the upright position. Triglyceride (TG) levels were increased by treatment in both groups (+20% and +22%, respectively; p less than 0.05), as were VLDL levels (+16% and +24%, respectively) although the rise in the latter was not significant. There were no significant differences in levels of HDL cholesterol (HDL-C), HDL, or apoproteins A and A1 (APO A, APO A1). Total cholesterol (TC) levels were increased by treatment in group I (+10%; p = 0.050) and decreased in group II (-9%, not significant), LDL-C being the principal fraction involved in these changes. There were no significant differences in levels of APO B. The ratio between TC and HDL-C levels remained unchanged. Given the current state of our knowledge concerning lipid markers for atherosclerosis, these results indicate that chronic administration of tertatolol may be considered devoid of 'atherogenic' effects.
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PMID:Tertatolol does not affect biochemical markers of atherosclerosis in normo- and hyperlipidemic hypertensive patients. 287 64

A variety of lipids, lipoprotein (Lp) lipids and APO-Lp were measured in 72 patients of both sexes suffering from cerebrovascular arteriopathy and compared with a control group matched for age and sex. The best discriminators by univariate analysis were serum concentrations of APO-AI, followed by APO-AII, high density lipoprotein phospholipids and HDL cholesterol (HDL-C). Low density lipoprotein cholesterol and serum APO-B values were lower in the patients than in the controls. With APO-AI only, patients and controls could be classified with 88-91% certainty. By combination of some of the variables which were selected by a stepwise discriminant analysis, several models were calculated resulting in 93-97% segregation of patients from controls. By multivariate analysis, APO-AI, APO-AII, HDL-C, and triglycerides in combination with the blood pressure or the body weight index were independent variables (in a mathematical sense). By comparing the present data with published results of previous studies it is concluded that cerebral atherosclerosis differs from other forms of atherosclerosis by several major risk indicators.
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PMID:Apolipoproteins AI, AII and HDL phospholipids but not APO-B are risk indicators for occlusive cerebrovascular disease. 309 38

Using a simple and rapid one-dimensional isoelectric focusing technique followed by immunoblotting, we have detected genetic polymorphism of human apolipoprotein C-II (APO C-II) in normal unfractionated plasma samples of individuals of black ancestry. Two common autosomal codominantly expressed alleles, designated APO C-II*1 and APO C-II*2, at the APO C-II structural locus have been observed with frequencies of 0.975 and 0.025 in US blacks and 0.943 and 0.049 in Nigerian blacks. In addition, the gene product of a rare allele designated APO C-II*3 was observed in a single Nigerian black. Apart from a single example of an APO C-II 2-1 phenotype in plasma samples from 187 whites, which was electrophoretically identical to the 2-1 phenotype observed in blacks, it appears that APO C-II*2 is a unique black marker of potential importance in anthropogenetic and atherosclerosis studies.
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PMID:Genetic studies of human apolipoproteins. III. Polymorphism of apolipoprotein C-II. 339 66

The possibility that Fas/APO 1 is involved in the apoptosis of advanced human coronary atherosclerosis was examined in the present study. Coronary arteries with atherosclerosis were obtained from human hearts with chronic ischemic heart disease at cardiac transplantation. Normal vessels were used as controls. Fas/APO 1 was detected by immunohistochemistry with a monoclonal antibody. Apoptotic cells were stained in situ by terminal deoxynucleotidyl transferase mediated-dUTP nick end labeling (TUNEL) and DNA fragmentation into oligonucleosomes was checked by gel electrophoresis. Bcl-2, an antiapoptotic oncoprotein, was detected by immunohistochemistry and Western blot. Apoptotic cells were present in the neointima in all stages of atherosclerosis, and in intraplaque small vessels. In initial lesions, only a few cells were undergoing apoptosis. By contrast, in advanced lesions, many cells were found to undergo apoptosis. Apoptosis was further confirmed by genomic DNA analysis using gel electrophoresis. Apoptotic cells were either smooth muscle cells or macrophages, but also endothelial and blood borne cells. Fas/APO 1 was present in foam cells. Most of the Fas/APO 1 positive cells were stained for the macrophage marker CD68 and for alpha-smooth muscle actin in serial sections. Several anti-Fas/APO 1 positive foam cells were revealed to undergo apoptosis by double staining. Bcl-2 was detected in Fas/APO 1 expressing plaques. A number of CD3-positive T-lymphocytes were found around foam cells expressing Fas/APO 1. This data suggests that Fas/APO 1 regulated apoptosis is involved in the development of advanced human atherosclerotic lesions and that it probably determines the amount of tissue mass in the diseased vessels.
Atherosclerosis 1997 Jun
PMID:The role of Fas/APO 1 and apoptosis in the development of human atherosclerotic lesions. 919 70

Elevated plasma levels of apolipoprotein A1 (APO-A1) and high-density lipoprotein cholesterol (HDL-C) are important protective factors for atherosclerosis and coronary heart disease. Using the data on plasma concentrations of APO-A1, and HDL-C particles HDL2-C and HDL3-C in 970 Israeli individuals belonging to 228 pedigrees, we tested the hypothesis that a major locus influencing interindividual variation in APO-A1 levels also controls interindividual variation in HDL3-C and HDL2-C levels. Univariate and bivariate complex segregation analyses, as implemented in two statistical packages (MAN-3 and PAP-4.0) were applied to test the hypothesis. The results of the analysis clearly indicated the possibility of major gene involvement in the determination of plasma concentration variation of each of the 3 study variables. The results provide strong evidence in support of our hypothesis that HDL3-C genetic variation fully depends on the APO-A1 major locus. In particular, environmental and sporadic models were strongly rejected (P < 0.001) in bivariate analysis. The hypothesis of no pleiotropic effect of the putative APO-A1 locus on HDL3-C transmission was also unequivocally rejected (P < 0.001), while the bivariate Mendelian model was accepted (P > 0.05). The results of bivariate analysis of APO-A1 effect on HDL2-C were not clear. They indicated the possibility of the existence of slight genetic covariation between the two variables, and as yet we were unable to decipher the mode of covariation with the applied models.
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PMID:Major locus influencing plasma APO-A1 levels also controls plasma HDL3-C concentrations. 959 11

The apolipoprotein(a) [APO(a)] gene encodes a protein component of lipoprotein(a) [LP(a)], whose plasma levels vary among individuals. To study the implications of LP(a), we examined plasma LP(a) levels and molecular weights of APO(a) in patients with cerebrovascular disease (CVD) or diabetes mellitus (DM). Mean LP(a) concentrations were higher in the CVD patients with atherothrombotic brain infarction than in those with brain hemorrhage and lacunar infarction. LP(a) levels were lower in the DM cases on diet therapy alone than in those treated with insulin or oral hypoglycemic agents. These results suggest that LP(a) is thrombogenic and atherogenic and that insulin may modulate LP(a) levels. We subclassified the APO(a) gene into four types (A to D) by polymorphisms in the 5'-flanking region. We also measured plasma LP(a) concentrations and examined expression of the gene by an in vitro assay. Homozygotes of type C had higher LP(a) levels than those of type D, and the relative expression of type C was higher than that of type D in vitro. Thus, LP(a) concentrations are genetically determined, and hyper-LP(a)-nemia is related to atherosclerosis and thrombosis.
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PMID:Apolipoprotein(a) and thrombosis: molecular and genetic bases of hyper-lipoprotein(a)-emia. 970 54

Tissue factor (TF) protein was overexpressed by macrophages and smooth muscle cells (SMCs) and deposited in the extracellular matrix of atherosclerotic intimas, probably resulting in enhanced procoagulant activity and the intimate participation in either thrombus formation or intimal fibrin deposition after the exposure of flowing blood and permeated fibrinogen to TF in atherosclerotic lesions. On the other hand, APO(a) was localized both in the stroma and within some macrophages. Fibrin deposition, which was more frequently detected in the matrix of advanced lesions than in that of early lesions, occasionally colocated with cell- and matrix-associated TF and APO(a) deposited in the matrix. These findings further support the hypothesis that the coagulation and fibrinolysis systems can play an essential role in the initiation and progression of atherosclerosis through fibrin deposition both in atherosclerotic plaques and on the arterial surface by neointimal hypercoagulability and a hypofibrinolytic state, which can also participate in SMC proliferation due to the decreased activation of TGF-beta by embedded and deposited APO(a). The clinical implications of these phenomena may thus contribute to future investigations in the prevention and treatment of atherosclerotic diseases.
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PMID:Atherosclerosis: coagulation and fibrinolysis. 970 57

Although coronary stenting reduces the incidence of post-angioplasty restenosis, it remains a problem. The influence of lipoproteins on the development of atherosclerosis has been demonstrated but their role in restenosis is controversial. Contradictory results have been published on the subject of the influence of the APO E genotype. In an initial study, the authors showed a closer correlation between Lp (a) and coronary artery disease in women than in men. A sub-group of women who underwent angioplasty and whose lipid profile had been well established, was analysed with respect to APO E alleles. The 59 patients who underwent angioplasty included 35 single, 20 twin and 4 triple vessel diseases. Control coronary angiography was performed in 40 of these women. A telephonic interview was carried out between 12 and 22 months after dilatation on the whole population. The apolipoproteins A1, B, Lp (a) and Lp A1 were measured by immunological, turbidimetric or electroimmunological techniques. The APO E genotyping was performed with the Inno-Lipa kit. The results showed 18 angiographic restenoses (Group A), 20 coronary artery disease without restenosis (Group B), 41 without angiographic (20) or clinical (21) restenosis (Group C). In Group A, the Lp (a) was well above the threshold value of 0.30 g/l. The e4 allele was associated with the highest values of total and LDL cholesterol fractions. There was no significant difference between the APO E genotype of the different groups or with respect to the severity of lesions. The authors conclude that if the e4 is more commonly associated with high LDL-cholesterol and Lp (a), its role in the process of restenosis remains unproven. A greater number of patients is required and further studies are desirable to determine the inflammatory and/or immunological mechanisms through which APO E could influence restenosis.
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PMID:[Influence of alleles of apolipoprotein E on restenosis after coronary angioplasty in women]. 989 30

An elevated plasma lipoprotein(a) (Lp(a)) concentration is an independent risk factor for coronary heart disease (CHD). Plasma Lp(a) levels are believed to be predominantly controlled by the APO(a) gene, which encodes the apo(a) glycoprotein moiety of the Lp(a) particle. However, other parameters in the lipoprotein profile as well as co-existing disease states or personal traits have been proposed as co-varieties. In order to examine these potential controlling factors in greater detail than previously possible, 1760 unrelated Caucasian subjects were studied, from which were identified 907 with a single expressing APO(a) allele. This strategy was followed to obviate the difficulty in dealing with the co-expression of different apo(a) isoforms and the resulting compound plasma Lp(a) level. After cube-root transformation of the plasma Lp(a) levels to normalise their distribution, a series of correlates were computed. There was no good correlation between Lp(a) concentration and any other measured lipid or lipoprotein in the lipid profile or with any other variable examined, with the important exception of the length of the expressed apo(a) isoform (r = -0.491, P = 0.0001). We conclude that in this population the plasma Lp(a) concentration is not predicted by the plasma lipid profile, alcohol intake, or smoking status but is predicted, albeit incompletely, by the length polymorphism of the APO(a) gene.
Atherosclerosis 1999 Apr
PMID:Predictors of plasma lipoprotein(a) concentration in the West of Scotland Coronary Prevention Study cohort. 1064 89


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