Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty postmenopausal women were randomly treated with desogestrel (DG) or levonorgestrel (LN) 125 micrograms/day for 3 weeks. Desogestrel reduced the serum total and free (non-protein bound) testosterone concentrations. It caused a small decrease in the sex hormone binding globulin capacity (SHBG) but did not influence the free testosterone index (testosterone/SHBG ratio). Levonorgestrel, on the other hand, did not influence the free testosterone concentration, but caused a significant increase in the free testosterone index. Levonorgestrel reduced the HDL and particularly the HDL2 cholesterol concentrations (mean change from 1.75 to 1.45 mmol/l for HDL and from 0.73 to 0.50 mmol/l for HDL2, P less than 0.001). It also caused a reduction in the VLDL triglyceride (P less than 0.05) but not the total serum triglyceride concentration. Desogestrel did not cause any significant changes in HDL or HDL2 cholesterol concentrations, but it reduced the VLDL triglyceride (P less than 0.01) and total serum (P less than 0.05) triglyceride concentrations. Neither of the two progestins influenced the postheparin plasma lipoprotein lipase (LPL) activity or the serum cholesterol esterification rate by lecithin:cholesterol acyltransferase (LCAT). It is therefore possible that both steroids decreased the hepatic output of triglycerides, which may be clinically important since both progestins are used in combination with ethinylestradiol (EE) which increases the hepatic TG synthesis. The failure of desogestrel to change HDL levels is consistent with earlier data on the lack of effects on HDL by non-androgenic progestins. Levonorgestrel increased the mean activity of postheparin plasma hepatic lipase (HL) from 23.3 to 28.0 mumol X h-1 X ml-1 (P less than 0.05). In contrast, this activity was not influenced by desogestrel. The magnitude of the changes in postheparin plasma HL activity and the free testosterone index (testosterone/SHBG ratio) showed significant positive correlation (+ 0.41, P less than 0.05). On the other hand, the changes in the HDL2 cholesterol and the postheparin plasma HL activity were inversely interrelated (r = 0.52, P less than 0.01). These relationships are consistent with the idea that the effects of different progestins on the HDL cholesterol are mediated by the sex steroid sensitive hepatic endothelial lipase.
Atherosclerosis 1985 Mar
PMID:Effects of two progestins with different androgenic properties on hepatic endothelial lipase and high density lipoprotein2. 315 21

The independent roles of human lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) in determining the distribution of apolipoprotein E (apo E) among the plasma lipoproteins has been studied in vitro. In one series of three studies, postheparin plasma (10%) was incubated for 2 h with autologous plasma and the changes in the lipoprotein association of apo E after lipase exposure were determined after lipoprotein fractionation on 4% agarose columns. Specificity for LPL or HTGL was achieved by inhibition with goat anti-human HTGL or with 1 M NaCl, respectively. In another study, LPL and HTGL were partially purified from human postheparin plasma. The independent effects of these enzymes on the lipoprotein association of apo E were then examined after incubation of plasma in the absence or presence of one or both lipases. Data from both types of in vitro study showed that LPL-mediated triglyceride hydrolysis in the absence of HTGL activity was accompanied by a loss of apo E from triglyceride-rich lipoproteins, a gain or no change in the apo E-containing lipoproteins the size of intermediate density lipoproteins (IDL) and inconsistent changes in the apo E mass associated with high density lipoproteins (HDL). HTGL activity, on the other hand, in the absence of LPL, resulted in a redistribution of apo E from lipoproteins the size of IDL and a gain by those of HDL size. These studies thus support previous in vivo studies which pointed toward a specific role for HTGL in the processing of apo E containing IDL.
Atherosclerosis 1988 Sep
PMID:Effect of lipoprotein lipase and hepatic triglyceride lipase activity on the distribution of apolipoprotein E among the plasma lipoproteins. 317 31

Two separate studies were carried out with acipimox, a new antilipolytic agent with long-lasting activity. First, in a randomized, double-blind, cross-over study a dose of 750 mg/day of acipimox versus placebo was employed for 60 days in 11 patients with type IV hyperlipoproteinemia. Mean plasma triglyceride levels were reduced after acipimox compared to placebo (434 +/- 60 vs 777 +/- 224 mg/dl, P less than 0.01). Serum total cholesterol fell also significantly after acipimox compared to placebo. No significant alteration was observed in the HDL2/HDL3 ratio or in the concentration or composition of the HDL subfractions. Six patients with severe hypertriglyceridemia (2 type IV and 4 type V) and low lipoprotein lipase (LPL) activity took part in a second, open study, lasting for 9 months. Acipimox was given at a dose of 750 mg/day for the first 6 months and 1200 mg/day for the last period. The response of serum total and VLDL triglycerides was inconsistent. HDL cholesterol was significantly raised (+33.3%) after 9 months of treatment due to changes of HDL2 and HDL3 cholesterol, phospholipid and protein concentrations. LPL activity was markedly reduced in adipose tissue at 9 months. No significant changes occurred in postheparin plasma LPL activity. In contrast, hepatic lipase activity showed a reduction of about 25% from 6 months of treatment onwards.
Atherosclerosis 1988 Feb
PMID:Effects of acipimox on serum lipids, lipoproteins and lipolytic enzymes in hypertriglyceridemia. 327 68

Eight male, normolipidemic, non-obese subjects were given fenofibrate (F) (300 mg daily) for eight days (period F). After a wash-out period of four weeks, phenobarbital (P) (100 mg daily) was given for eight days (period P). At the end of this period, P was continued at the same dosage but F (300 mg daily) was added and both drugs were given simultaneously for a further eight-day period (period P + F). The plasma concentrations of lipids and the plasma activities of enzymes involved in the interconversion of plasma lipoproteins: lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyltransferase (LCAT) were measured before and at the end of each period of treatment. Fenofibrate induced a decrease in the plasma concentration of triglycerides (TG), total cholesterol (TC), apoB and an increase in the plasma activities of LPL and LCAT. Phenobarbital induced a decrease in the plasma concentration of TC, HDL-C and LDL-C (with an unchanged HDL-C/LDL-C ratio) and in the plasma activity of LPL. Addition of P to F did not modify the hypolipidemic action of F but the increase of LPL activity during period P + F was found to be greater than that observed during period F. It is concluded that P does not modify the serum lipoprotein pattern in a way which can be considered as beneficial in terms of atherosclerosis. By measuring the serum concentration of unconjugated bilirubin, the plasma clearance of antipyrine and the urinary excretion of 6 beta-hydroxycortisol as parameters of hepatic microsomal induction, F appeared to be a slight inducer as compared with P. Thus, enzyme induction cannot explain the changes in serum lipoproteins induced by P and does not modify the hypolipidemic action of F.
 ...
PMID:Changes in plasma activities of lipolytic enzymes and lipids of normolipidemic subjects given phenobarbital, a strong microsomal inducer, alone or in combination with fenofibrate. 341 May 96

Patients treated with corticosteroids often have a dyslipoproteinemia characterized by elevated plasma levels of triglyceride and low density lipoprotein cholesterol and/or decreased levels of the high density lipoprotein2 fraction of high density lipoprotein cholesterol. This study was undertaken to determine if such patients also have elevated apolipoprotein-B (apoB) levels and/or abnormalities of the activities of the triglyceride lipases in postheparin plasma. Plasma lipoprotein levels and the postheparin activities of hepatic lipase and lipoprotein lipase were measured in 28 women with systemic lupus erythematosus (SLE) who were treated with prednisone, 10 women with SLE not treated with prednisone, and 15 normal women. The prednisone-treated group had higher mean plasma levels of triglyceride [2.06 +/- 1.3 (+/- SD) vs. 1.15 +/- 0.35 and 0.95 +/- 0.46 mmol/L; P less than 0.01], low density lipoprotein cholesterol [3.41 +/- 1.4 (+/- SD) vs. 2.79 +/- 0.67 and 2.84 +/- 0.70 mmol/L; P less than 0.01], and apoB [1.16 +/- 0.35 (+/- SD) vs. 0.82 +/- 0.13 and 0.76 +/- 0.22 g/L] than the other 2 groups. Forty-three percent of the prednisone-treated group had apoB levels of 1.20 g/L or more compared to 7% of normal subjects and none of the untreated SLE group (P less than 0.05). However, of the 12 prednisone-treated patients with elevated plasma apoB levels 5 had normal plasma lipid levels. There were no differences in the postheparin lipase activities among the 3 groups. These data indicate that corticosteroid-treated patients have elevations in apoB as well as hyperlipidemia. The lipoprotein abnormalities may explain the increased risk of atherosclerosis reported in these patients.
 ...
PMID:Elevated apolipoprotein-B levels in corticosteroid-treated patients with systemic lupus erythematosus. 341 Sep 32

To study exogenous fat metabolism, we used the vitamin A-fat loading test, which specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). Postprandial RP concentrations were followed in total plasma, and chylomicron (Sf greater than 1,000) and nonchylomicron (Sf less than 1,000) fractions. In normal subjects postprandial lipoproteins were present for more than 14 h, and chylomicron levels correlated inversely with lipoprotein lipase activity and fasting high density lipoprotein (HDL) cholesterol levels and nonchylomicron levels correlated inversely with hepatic triglyceride lipase activity. The main abnormality in type IV patients was a 5.6-fold increase in the chylomicron fraction, whereas in type III patients it was a 6.4-fold increase in nonchylomicrons. Type IIa patients had abnormally low chylomicron fractions. In type IV patients gemfibrozil decreased, whereas in type IIa patients cholestyramine increased the chylomicron fraction 66 and 88%, respectively. This study demonstrates an unexpectedly large magnitude and long duration of postprandial lipemia in normal subjects and patients. These particles are potentially atherogenic, and their role in human atherosclerosis warrants further study.
 ...
PMID:Different patterns of postprandial lipoprotein metabolism in normal, type IIa, type III, and type IV hyperlipoproteinemic individuals. Effects of treatment with cholestyramine and gemfibrozil. 347 Mar 6

There is a very high probability that lipoprotein metabolism plays a central role in the etiology of coronary heart disease. In sedentary persons one way to favorably alter lipoprotein metabolism and possibly delay the progression of coronary atherosclerosis is by an increase in their habitual physical activity. More physically active persons tend to have lower plasma triglycerides and very low density lipoprotein concentrations, and a greater high-density lipoprotein mass due to higher concentrations of the subfraction HDL2 and apoprotein A-I. Plasma low-density lipoprotein concentrations usually are not significantly reduced by exercise unless accompanied by weight loss, but there may be important changes in the distribution among the low-density subfractions. These exercise effects are most likely mediated by alterations in the activity of enzymes involved in the synthesis, transport and catabolism of the various lipoproteins including lipoprotein lipase, hepatic lipase and lecithin: cholesterol acyltransferase. In healthy persons as well as in patients with ischemic heart disease, diabetes and renal failure, an increase in moderate-intensity, endurance-type activity requiring an expenditure of approximately 4 MJ (1,000 kcal) per week usually produce favorable lipoprotein changes. Above this level a dose-response relationship exists, with greater changes occurring up to energy expenditures of 19 MJ (4,500 kcal) per week.
 ...
PMID:The influence of exercise training on plasma lipids and lipoproteins in health and disease. 353 12

Feline serum lipoproteins were fractionated into four distinct classes by density gradient ultracentrifugation and characterized with respect to physical and chemical properties. The distribution of serum lipids, lipoproteins and apolipoproteins was quite unlike that in man, the cat having five times as much high density lipoproteins (HDL) as low density lipoproteins (LDL). The lipoproteins in the d less than 1.019 g/ml fraction of cats were larger and were richer in triglycerides than their human counterparts and contained a considerable amount of beta-migrating particles. The low density lipoproteins of cats and man had similar chemical composition, but cat LDL had a higher negative charge, were smaller and contained apoprotein A-I. Cat HDL consisted of two distinct subfractions HDL2 and HDL3 with similar density boundaries and particle size as in man. In cat serum and HDL fraction apoprotein A-II was a minor component. Like human serum, fasting cat serum contained only the larger species of apoprotein B, apo B-100, whereas intestinal lymph contained exclusively the smaller apo B-48. Post heparin feline and human plasma possessed both lipoprotein lipase and hepatic lipase. Chylomicrons formed after a fat load in cats were removed from the circulation as rapidly as in man. It is concluded, that the cat is another animal model of potential interest for the study of lipoprotein metabolism.
Atherosclerosis 1987 Jul
PMID:A study of the lipid transport system in the cat, Felix domesticus. 363 43

Cynomolgus monkeys (Macaca fascicularis) fed monkey chow (n = 10) had a mean +/- SD post-heparin plasma lipoprotein lipase (LPL) activity level (14.7 +/- 5.5 units/ml) similar to that found in human beings (15.7 +/- 3.9 units/ml). However, the hepatic triglyceride lipase (H-TGL) in these monkeys was extremely low (0.5 +/- 0.3 units/ml) when compared with that in human beings (10.9 +/- 4.3 units/ml). The consumption of isocaloric atherogenic diets (0.2 mg cholesterol/Cal) with either saturated (P/S = 0.34) or polyunsaturated (P/S = 2.2) fat led to increased LPL activity levels (27.6 +/- 6.5 and 28.8 +/- 16.1 units/ml, respectively) and the accumulation of plasma low density lipoprotein cholesterol (LDL-C). The results indicate that cholesterol-containing atherogenic diets with either primarily saturated or polyunsaturated fat have similar potential for the increase of LPL activity. However, it is not clear whether the high dietary cholesterol content represents an obligatory component for the increase of LPL. We speculate that the high level of LPL in cynomolgus monkeys when fed a cholesterol-rich, high fat diet could be a contributing factor to the accumulation of excessive plasma LDL-C.
Atherosclerosis 1987 Oct
PMID:Effect of atherogenic diet on lipoprotein lipase activity in cynomolgus monkeys. 367 12

Relations between lipoprotein fractions, lipoprotein lipase activities, thyroid hormones and coronary lesion growth were studied among 35 male patients with severe coronary atherosclerosis, who had participated in the lipid lowering, dietary Leiden Intervention Trial. Coronary arteriographies were performed at the beginning of the study and 2 years later at termination. The coronary anatomy was quantitated with a computer-based analysis system to assess the progression rate of coronary atherosclerosis on the basis of the absolute arterial dimensions in a patient's coronary tree; for these purposes an absolute coronary score was computed. On the basis of the absolute coronary scores, the entire group of patients could be divided into a no lesion growth group (14 patients) and a progression group (21 patients). Lipoprotein fractions, lipoprotein lipases and thyroid hormones were determined at the end of the trial. No significant difference was found between the no lesion growth and progression groups of patients for total cholesterol (TC) and LDL-cholesterol (LDL-C). The VLDL-cholesterol (VLDL-C) and triglycerides (TG) were significantly higher (P less than 0.05) and HDL-C was almost significantly lower (P less than 0.10) in the progression group. Hepatic lipase (HL) values were significantly higher in the no lesion growth group, as compared to the progression group, whereas lipoprotein lipase (LPL) values were not significantly different. Triiodothyronine (T3) was significantly lower (P less than 0.01) in the progression group. Multivariate regression analysis showed HL to be the most important determinant of changes in coronary atherosclerotic lesions. T3 and HDL were also independently inversely related to coronary atherosclerotic lesion growth.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1987 Nov
PMID:Progression and regression of human coronary atherosclerosis. The role of lipoproteins, lipases and thyroid hormones in coronary lesion growth. 368 83


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>