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)

The fatty acid composition of the plasma lipid esters has been studied during lipid-lowering treatment of 95 patients with atherosclerotic disease. During the first two months of the trial only a diet was prescribed. During the ensuing two months either clofibrate or niceritrol, a nicotinic acid ester, was added in a randomized order. During the last two months the second drug was added. The combined treatment with diet, clofibrate and niceritrol caused highly significant serum lipid reductions. The fatty acid composition in the plasma lipid esters was determined in samples from each trial period to measure the degree of dietary adherence. During dietary treatment the relative content of saturated and monounsaturated fatty acids secreased and the polyunsaturated fatty acids increased with an increasing ratio between pulyunsaturated and saturated fatty acids (P/S ratio) in the cholesterol esters and triglycerides. Only minor changes were seen in the phospholipids. The changes caused by the diet were partly reversed by clofibrate while niceritrol did not cause any major changes of the fatty acid composition. Clofibrate treatment coincided with increasing amounts of monounsaturated fatty acids, especially oleate (18 : 1), in the cholesterol esters, triglycerides and phospholipids while there were significant reductions of the content of linoleic (18 : 2) acid in both the cholesterol esters and triglycerides. The 18 : 2/18 : 1 ratio decreased significantly in all the lipid esters analyzed. However, the P/S ratio was not significantly affected, partly because the relative content of saturated fatty acids also tended to decrease during clofibrate treatment. It is concluded that addition of clofibrate treatment to patients who are on a diet enriched with polyunsaturated fats is associated with a change from polyunsaturated to monounsaturated fatty acids in the plasma lipid esters but does not significantly effect the ratio between polyunsaturated and saturated fatty acids. The fatty acid changes caused by clofibrate treatment and counteracted by an increased amount of polyunsaturated fat in the diet.
Atherosclerosis 1980 Jan
PMID:Changes in the fatty acid composition of the plasma lipid esters during lipid-lowering treatment with diet, clofibrate and niceritrol. Reduction of the proportion of linoleate by clofibrate but not by niceritrol. 698 77

In an effort to reduce serum lipids in patients with atherosclerotic manifestations, a combined treatment with a conventional lipid-lowering diet, clofibrate and niceritrol was used. The effect on glucose metabolism of such treatment was studied. Among the 106 patients 66 took the full dose of both drugs and of these 51 were weight-stable and non-diabetic. The effects of the diet and the drugs were evaluated in this subsample. Diet had no effect on fasting blood glucose concentration, the K value of an intravenous glucose tolerance test (IVGTT) and concentrations of serum insulin. Niceritrol treatment was associated with increased blood glucose, decreased K value, elevated fasting serum insulin and serum insulin at 60 min during IVGTT. Clofibrate had the opposite effects to niceritrol and when both drugs were combined, carbohydrate metabolism was unchanged compared with the pre-treatment state.
Atherosclerosis 1982 Jun
PMID:Changes in glucose tolerance and plasma insulin during lipid-lowering treatment with diet, clofibrate and niceritrol. 705 96

The effect of CH-123 (3-carbethoxy-6-methyl-1-9-(carboxy-methyl)-1-4-oxo-6,7,8,9-tetrahydro-4H-pyrid o(1,2a)pyrimidine) was investigated on the activity of 4 lysosomal enzymes: beta-glucuronidase, beta-galactosidase, N-acetyl-beta-glucosaminidase and acid phosphatase obtained from aortic smooth muscle and liver cells of rabbits. Animals were fed on a 2% cholesterol diet for 4 weeks and used an experimental atherosclerotic group. In drug-treated groups, after 4 weeks of cholesterol feeding the diet was changed to regular food and the animals were treated daily either with 50 mg/kg CH-123 or with 250 mg/kg Clofibrate. The postnuclear supernatant of homogenates of liver and aortic cells was isolated, lysosomes were fractionated by sucrose density gradient centrifugation, and the activity of enzymes was measured. In cholesterol-fed animals the enzyme activities of aorta and liver was 3-5 times higher than in the control, i.e. in the group of rabbits fed regular food. On Clofibrate treatment the enzyme activities were 2-3 times higher, but on treatment with CH-123, they were only 1.2-1.8 times above the control. Experiments suggest that CH-123 treatment suppresses the elevated lysosomal marker enzyme activities in aortic and liver cells of atherosclerotic animals.
Atherosclerosis 1981 May
PMID:Effect of CH-1243, a pyrido (1,2-a) pyrimidine derivative on the elevated activity of lysosomal enzymes of rabbit aorta and liver in experimental atherosclerosis. 724 98

The effect of clofibrate on the same subjects in similar test conditions were used as a control to verify the alleged beneficial effects from garlic and onion on alimentary hyperlipemia in normals and in cases with ischemic heart disease. The results showed that clofibrate checked the fat-induced (a) rises of serum triglyceride and plasma fibrinogen, and (b) falls of coagulation time (CT) and blood fibrinolytic activity (BFA). Only garlic had a clofibrate-like effect on CT but both garlic and onion checked the postprandial fall of BFA. Clofibrate, however, increased BFA even above the fasting level. Serum cholesterol and beta-lipoprotein were not appreciably affected by fat with or without any drug. Thus, surprisingly, the so-called beneficial effects of garlic and onion were not seen in subjects who had shown significant changes after clofibrate.
Atherosclerosis 1981 Jul
PMID:Comparative effect of clofibrate, garlic and onion on alimentary hyperlipemia. 725 24

Serial liver biopsies were carried out in 67 patients with HLP and/or fatty liver before, during short- and long-term therapy with CPIB and after termination of therapy. Results (1) Decrease of liver glycogen from 4.17% to 2.69% (wet weight, P less than 0.02). (2) Insignificant changes of liver triglyceride content. (3) Significant decrease of manganese, while the concentrations of zinc and copper in the liver biopsy specimens remained unchanged. (4) No signs of liver intoxication or cancerogeneous effects of light-microscopic pictures. (5) Significant increases in numbers of mitochondria and cristae as well as a hypertrophy of endoplasmic reticulum with longer lasting therapy. (6) Striking focal proliferation of cristae mitochondriales in 3 cases on longterm treatment. (7) Regression of the mitochondrial alterations after termination of the CPIB therapy. Our findings suggest that an increased number of mitochondria and of their inner membranes in the liver cells induced by CPIB could play an important role in the hypolipidemic action of the drug.
Atherosclerosis 1980 Jun
PMID:Effects of p-chlorophenoxyisobutyric acid (CPIB) on the human liver. 740 47

Lipid and lipoprotein concentrations, including high density lipoproteins (HDL) and its subfractions, were contrasted in subjects with Type IV hyperlipoproteinemia, before and after therapy with clofibrate. Very low density lipoprotein (VLDL) levels were raised, whereas both low density lipoprotein (LDL) and HDL values were reduced in the patient group. Clofibrate reversed this trend and VLDL cholesterol and protein levels fell to approximate control values. LDL and HDL cholesterol increased but remained significantly lower than in normal controls. However, LDL and HDL protein did approach control values. Of the HDL subfractions, HDL-3 was significantly reduced in the group with Type IV hyperlipoproteinemia. Clofibrate resulted in a significant increase in the HDL-2: HDL-3 cholesterol ratio, but had only a modest effect on HDL-3 concentrations. HDL-3 may be the critical HDL subfraction responsible for the inverse correlation between levels of HDL and the development of ischemic heart disease.
Atherosclerosis 1980 Aug
PMID:The concentration of high density lipoprotein in patients with type IV hyperlipoproteinemia and the effect of clofibrate. 741 65

The effects of probucol treatment on cholesterol metabolism were examined in rats. Male Sprague-Dawley rats were divided into 3 groups: one group was given 0.25% probucol containing chow diet, one group was given 0.25% clofibrate containing chow diet, and the third group was fed chow diet alone. All groups of rats were maintained on these regimens for 4 weeks before killing. Probucol treatment resulted in a decrease in plasma cholesterol and cholesterol 7 alpha-hydroxylase activity. Clofibrate treatment resulted in a reduction of plasma cholesterol, hepatic HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities. The fecal excretion of neutral and acidic sterols were decreased significantly in the probucol or clofibrate-treated rats. In the bile there was a decrease in the concentration of total bile acids. These results suggest the mechanism for hypocholesterolemic action of probucol to be different from that of clofibrate.
Atherosclerosis 1980 Aug
PMID:Effect of probucol on cholesterol metabolism in the rat. 741 72

Clofibrate has cholesterol- and triglyceride-lowering effect. They affect on the various points in the metabolic pathway of lipoproteins. They improve VLDL-synthesis in liver and increase the activity of LPL and hepatic TG lipase. As the results, HDL-cholesterol increases and LDL decreases. Therefore Clofibrate decreases not only plasma triglyceride but cholesterol levels. It has been reported that Clofibrate have a preventive effect on cardiovascular disease. So these agents are useful in the treatment for hyperlipidemic patients with or without atherosclerosis.
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PMID:[Clofibrate treatment of hyperlipoproteinemia]. 785 24

Clofibrate is a lipid-profile modifying agent belonging to the fibrate class of drugs. Fibrates are known to exhibit their beneficial effects by activating peroxisome proliferator-activated receptor-alpha (PPARalpha) and used in the treatment of dyslipidemia and atherosclerosis and for the prevention of heart failure. Hereby, the preparation of two new sets of clofibrate analogues, ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates and ethyl 2-(4-chlorophenoxy)-3-hydroxyalkanoates is described starting from commercially available 3-oxoalkanoates in fair to good yields. Treatment of 3-oxoalkanoates with SO2Cl2 yielded the corresponding 2-chloro-3-oxoalkanoates, that were then converted into 2-(4-chlorophenoxy)-3-oxoalkanoates by reacting with sodium or caesium 4-chlorophenate. Reduction of the keto group with NaBH4 afforded the corresponding 2-(4-chlorophenoxy)-3-hydroxyalkanoates in very high yields and with variable diastereoselectivity. Biological evaluation of the compounds was performed by a transactivation assay in a transiently transfected monkey kidney fibroblast cell line. The newly synthesised clofibrate analogues failed to show noticeable levels of PPAR activation at concentrations where clofibrate showed an evident activity, suggesting that the structural modifications caused the loss of PPAR activity.
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PMID:Synthesis and biological evaluation of new clofibrate analogues as potential PPARalpha agonists. 1569 49

Homocysteine (Hcy) is a risk factor for atherosclerosis. It is generally accepted that inducible nitric oxide synthase (iNOS) is a key enzyme in the regulation of vascular disease. The aim of the present study is to investigate the effects of peroxisome proliferator-activated receptor ligands on iNOS in the presence of Hcy in human monocytes. Foam cells, induced by oxidize low density lipoprotein (ox-LDL) and phorbol myristate acetate (PMA) in the presence of different concentrations of Hcy, clofibrate and pioglitazone in human monocytes for 4 d, were examined by oil red O staining. The activity of iNOS was detected by real-time quantitative reverse transcription-polymerase chain reaction and Western blot analysis. The capability of DNA methylation was measured by assaying endogenous C5 DNA methyltransferase (C5MTase) activity, and the iNOS promoter methylation level was determined by quantitative MethyLight assays. The results indicated that Hcy increased the activity of C5MTase and the level of iNOS gene DNA methylation, resulting in a decrease of iNOS expression. Clofibrate and pioglitazone could antagonize the hcy effect on iNOS expression through DNA methylation, resulting in attenuation of iNOS transcription. These findings suggested that Hcy decreased the expression of iNOS by elevating iNOS DNA methylation levels, which can repress the transcription of some genes. Peroxisome proliferator-activated receptor alpha/gamma ligands can down-regulate iNOS DNA methylation, and could be useful for preventing Hcy-induced atherosclerosis by repressing iNOS expression.
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PMID:Ligands of peroxisome proliferator-activated receptor inhibit homocysteine-induced DNA methylation of inducible nitric oxide synthase gene. 3252 39


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