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)

Twelve male patients with hyperlipoproteinemia were treated with clofibrate, 1 g twice daily. Serum triglyceride concentration decreased on the average 28 +/- 6%. No significant change of serum cholesterol concentration occurred. Post heparin plasma lipoprotein lipase activity isolated and partially purified by heparin Sepharose affinity chromatography was determined quantitatively. During the clofibrate treatment this enzyme activity increased 48 +/- 9%. The post heparin hepatic triglyceride lipase did not change significantly. The possibility that the serum triglyceride-lowering effect of clofibrate might partly be explained by an increased removal rate of triglyceride rich lipoproteins through increased lipoprotein lipase activity is discussed.
Atherosclerosis 1977 Aug
PMID:The effect of treatment with clofibrate on hepatic triglyceride and lipoprotein lipase activities of post heparin plasma in male patients with hyperlipoproteinemia. 88 4

Two trioleoyl glycerol hydrolases, one of lysosomal origin as determined by a high correlation with the lysosomal marker enzyme, N-acetyl-beta-glucosaminidase, and one having the characteristics of lipoprotein lipase, were measured at varying stages of lesion development in the aortas of cholesterol-fed rabbits. Both lipases were greatly enhanced in atheromatous aortas and were linearly related to lesion severity as measured by total aortic cholesterol. Lipoprotein lipase activities of myocardium and of plasma of cholesterol-fed rabbits were also significantly increased relative to controls. The data suggest that lipoprotein lipase might be a factor regulating cholesterol deposition in the aorta.
Atherosclerosis 1977 Jun
PMID:Effect of cholesterol feeding on arterial lipolytic activity in the rabbit. 90 18

Lipoprotein lipase (LPL) activity was measured in adipose tissue, heart and diaphragm in Sprague--Dawley rats after estrogen therapy or orchiectomy. Enzyme activity was measured by incubation of tissue fragments with a triolein emulsion in the presence of serum and heparin. In confirmation of other work, depression of adipose tissue LPL followed estradiol treatment in pharmacologic or near-physiologic doses. Cardiac and diaphragmatic muscle LPL were increased. Estrogen-treated male animals showed growth retardation. However, they gained weight steadily and did not show significant differences in serum insulin, glucose of D-beta-hydroxybutyrate. The effects of estradiol in male animals were reversed by sequential fasting and re-feeding. At times during growth and aging in normal female rats, adipose tissue activity was decreased while cardiac and skeletal muscle activities were increased relative to males of the same age or body weight. Castration of male rats failed to reproduce the effect of estrogens on tissue lipoprotein lipase. These in vitro data suggest that exogenous estrogens may shift the flux of triglyceride fatty acids from storage in the adipose organ toward incorporation by muscle. These, and other data, raise the possibility that physiological estrogen secretion exerts a tonic influence over the synthesis and ultimate destination of triglyceride fatty acids.
Atherosclerosis 1976 Sep
PMID:Estrogen treatment and gonadal function in the regulation of lipoprotein lipase. 97 48

Human post-heparin plasma contains at least two different triglyceride lipases (TGL). The plasma lipolytic activity has been attributed to extra-hepatic and hepatic origin. Both post-heparin triglyceride lipases were partially purified and characterized. With heparin-Sepharose 4 B affinity chromatography it was possible to partially purify human adipose tissue lipoprotein lipase (LPL) as well as a lipase from human liver. The effects of NaCl, pre-heparin plasma, pH and temperature on these two tissue lipases and plasma lipases were studied in parallel. Antibodies were produced against plasma hepatic triglyceride lipase (plasma H-TGL) that did not cross react with LPL. TGL activity of human liver was completely inhibited by antibodies against plasma H-TGL. From these results it appears that human post-heparin plasma contains two triglyceride lipase activities which originate from liver and extra-hepatic tissues such as adipose tissue.
Atherosclerosis
PMID:A comparative study of human tissue and post-heparin plasma triglyceride lipases. 100 6

Rat heart lipoprotein lipase was highly purified by affinity chromatography using heparin-Sepharose 4B. When extracts of acetone powder were applied to columns, lipase activity was firmly bound to the gel matrix and was later eluted with 1.5 M NaCl. At this stage the eluted enzyme was purified 1500-fold. Disc gel electrophoresis yielded a single protein band corresponding with the enzyme activity. The apparent molecular weight was 60,000. The purified enzyme was highly unstable; however, its activity could be partially stabilized by glycerol or ethylene glycol. In studying the purified enzyme we observed: (i) a cofactor in serum was required for full enzymatic activity; ApoLp-Glu could be substituted for this cofactor; (ii) ApoLp-Ser was inhibitory to lipase activity; (iii) NaCl and protamine sulfate also markedly inhibited the lipase activity; (iv) heparin stimulated the enzymatic activity.
Atherosclerosis
PMID:Rat heart lipoprotein lipase. 120 Nov 47

Published data have suggested that hypertriglyceridemia in obesity may result from the combination of hepatic overproduction and diminished removal of triglyceride-rich lipoproteins. Diminished catabolism might be expected if tissue lipoprotein lipase activity were decreased, a finding which has been reported in biopsies of adipose tissue from obese subjects. Abnormalities in heparin-released triglyceride lipase activity (PHLA) in obesity have not been reported, however. We have examined the possibility that methods for the measurement of PHLA might have failed to reveal such a defect because of the disproportionality between plasma volume and increasing body mass in obesity. Since it is usual to administer heparin on the basis of body weight, higher plasma heparin levels would be achieved in obese individuals. We performed standard PHLA assays in lean and obese volunteers. In the obese, heparin levels were consistently higher than in lean individuals although PHLA values were similar in both. Thus, PHLA in obesity appeared to be inappropriate for the heparin levels attained in plasma. Pharmacokinetic studies suggest that a decrease in PHLA available for release by heparin rather than heparin insensitivity underlies this phenomenon.
Atherosclerosis
PMID:Abnormal post-heparin lipolytic activity in obesity. A preliminary note. 120 Nov 46

A method for the assay of lipoprotein lipase activity (LPLA) in heparin eluates of needle biopsies of adipose tissue is presented. A serum activated phosphatidestabilized emulsion of labelled triolein has been used as substrate. This method and a previously described method using heparin eluates as enzyme source and a commercial triglyceride emulsion, Ediol, as substrate, showed a high degree of correlation (correlation coefficient = 0.94) when parallel determinations were performed on biopsies from 16 subjects. Further, the Ediol method similarly correlated well with a method for LPLA assay, previously described by Nilsson-Ehle and Belfrage, on acetone-ether extracts of adipose tissue (correlation coefficient = 0.88; 19 subjects).
Atherosclerosis
PMID:A study of different methods for the assay of lipoprotein lipase activity in human adipose tissue. 120 Nov 44

Exercise training alters plasma lipoprotein profiles in a manner compatible with decreased coronary artery disease risk. The aim of this study was to ascertain whether interruption of training (detraining) was associated with potentially undesirable changes in the metabolism of post-prandial lipoproteins and plasma levels of Lp(a). Eight normolipidemic, male runners who ran 30-40 miles/week were studied in the trained state and after 14-22 days of detraining. Two of the subjects were studied in the reverse order to control for any confounding effects of exercise sequence. Detraining resulted in (1) a 12% (P = 0.002) reduction in the subjects' aerobic capacity, (2) a 7.7% (P = 0.007) reduction in fasting concentrations of high density lipoprotein cholesterol (HDL-C), (3) a 21% (P = 0.01) reduction in post-heparin lipoprotein lipase activity. Lp(a) concentrations did not change significantly (mean increase 15%, P = 0.076). Fasting plasma concentrations of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) did not change in the detrained state. There was little fluctuation over 24 h in plasma concentrations of TC, LDL-C and HDL-C in either the trained or detrained states. TG concentrations fluctuated over the 24 h in accord with food intake, but there were no exercise-related changes. Exercise had a dramatic effect on chylomicron and chylomicron remnant metabolism as measured by retinyl palmitate measurements. The mean areas under the concentration vs. time curves (AUC) for chylomicron-retinyl esters increased by 41% (P = 0.013) and for chylomicron remnant-retinyl ester by 37% (P = 0.058) following detraining.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1992 Aug
PMID:Short-term interruption of training affects both fasting and post-prandial lipoproteins. 141 92

An increased risk of developing premature atherosclerosis is associated with stress, diabetes, obesity, and hypertension. These conditions are associated with insulin resistance, hyperglycemia, hypertriglyceridemia and hypercholesterolemia. An alternative way of interpreting insulin resistance is to consider that metabolism in this condition would be regulated to a greater extent by stress hormones and in particular by cortisol. Glucocorticoids and fatty acids (which are produced in response to stress) antagonise the actions of insulin in promoting glucose uptake and protein synthesis, in decreasing gluconeogenesis and protein catabolism, and promoting the clearance of intermediate density lipoprotein and low density lipoprotein from the circulation by the liver. They also promote the secretion of very low density lipoprotein thus producing hypertriglyceridemia and hypercholesterolemia. By contrast to this antagonism, cortisol can also facilitate the action of insulin in stimulating the storage of energy via glycogen and fatty acid synthesis and through lipoprotein lipase in adipose tissue. These effects are significant in relation to obesity and to weight gain. An increased control of metabolism by cortisol therefore produces changes in metabolism that are potentially atherogenic and it is associated with insulin resistance and the other risk factors for atherosclerosis. Benfluorex treatment improves insulin sensitivity and has antihyperglycemic and hypolipidemic effects in human beings and in experimental animals. These effects can be observed independently of weight loss, but lowering food intake also produces a metabolic benefit. Long-term treatment with benfluorex can also decrease stress responses in terms of glucocorticoid release and the stimulation of lipolysis probably by its serotoninergic control of the hypothalamic-pituitary-adrenal axis. Such an action provides for an integrated treatment of the obese-diabetic-hyperlipidemic syndrome. Benfluorex produces overall changes in metabolism that tend to normalise the major risk factors associated with premature atherosclerosis. This provides a potential advantage over other therapies for atherosclerosis which may ameliorate a symptom (e.g., hyperlipidemia) without treating the underlying metabolic disturbance that predisposes to atherogenesis.
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PMID:[Mode of action of benfluorex. Recent data]. 143 2

Association studies were carried out on a sample of 87 patients from Sweden who had survived a myocardial infarction (MI) at a young age and 93 age-matched healthy individuals, to compare the impact of polymorphisms (PvuII, HindIII and Serine447-Stop) at the lipoprotein lipase (LPL) gene locus on among-individual differences in plasma lipid traits and progression of atherosclerosis. Significant linkage disequilibrium was detected between any two of these polymorphisms, with the Stop447 allele being only found on the same chromosome as the rare alleles (no cutting sites) of the PvuII and HindIII polymorphisms. In the healthy individuals, weak associations were found between genotypes of the HindIII polymorphism and triglycerides and the PvuII polymorphism and high density lipoprotein cholesterol explaining 7.4% and 5.6% of sample variance (P = 0.03 and 0.09), respectively. No associations were found between these traits and genotypes of the Serine447-Stop substitution, and thus it is unlikely to be the cause of the associations seen with the PvuII and HindIII polymorphisms even though it truncates the enzyme amino acid sequence. The presence of the rare allele, H-, of the HindIII polymorphism was associated with a smaller variance in triglycerides and both cholesterol and triglycerides in the very low density lipoprotein fraction, and with larger interdependent variation between these lipid traits, and also between LPL activity and these lipid traits. This implies that the H- allele, rather than the Stop447 allele, has the major impact on interdependence between traits which are directly or indirectly influenced by LPL activity. In the healthy individuals who were carriers of the apolipoprotein E2 allele, the inter-dependence between LPL activity and lipid traits was significantly smaller, and that between high density lipoprotein cholesterol and both cholesterol and triglycerides in the very low density lipoprotein fraction was much larger compared with non-carriers (P < 0.05). No significant associations were found between lipid traits or lipase activity and genotypes of the Serine447-Stop substitution. However, in the patients, global severity of coronary atherosclerosis at the first angiography was significantly associated with haplotype combinations of the HindIII and the Serine447-Stop polymorphisms, with the H-Stop haplotype being associated with the highest median score (P = 0.02). The data suggest that variation at the LPL gene locus is associated with a pleiotropic effect, that is not directly mediated by changes in lipids, on severity of coronary atherosclerosis.
Atherosclerosis 1992 Dec
PMID:Associations between lipoprotein lipase gene polymorphisms and plasma correlations of lipids, lipoproteins and lipase activities in young myocardial infarction survivors and age-matched healthy individuals from Sweden. 146 62


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