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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma lipoprotein and liver lipid composition, and the lipid, cholesterol and apolipoprotein synthesis have been studied in normal and diet-induced hyperlipidemic rats, receiving ciprofibrate (2.5 mg/kg body weight) or fenofibrate (50 mg/kg b.w.) for 8 days. Ciprofibrate is about 25-fold more active than fenofibrate in reducing plasma triglyceride and cholesterol concentrations both in normolipemic and in hyperlipemic rats. In normolipemic rats ciprofibrate reduced the concentration and the lipid content of all lipoprotein classes. The incorporation of [14C]palmitate and [3H]leucine into the lipoproteins was reduced by ciprofibrate and fenofibrate. The reduction in lipoprotein production was confirmed by prevention of Triton-induced hyperlipemia. Liver and plasma cholesterol synthesis estimated by 3H2O and [14C]mevalonate incorporation indicated an inhibitory effect on HMG-CoA reductase. Administration of ciprofibrate or fenofibrate to rats fed a fat and cholesterol-rich diet partially prevented liver steatosis and hyperlipemia. Both drugs reduced the overproduction of lower density lipoproteins. The ratio of (VLDL + LDL)-cholesterol/HDL-cholesterol which was increased by the diet alone from 0.4 (normal) to 11 remained close to the normal value in the animals receiving ciprofibrate. In the hyperlipemic animals, ciprofibrate reduced the incorporation of [3H]oleate into the liver and plasma glycerolipid and increased cholesterol esterification. Ciprofibrate efficiently reduces plasma levels of cholesterol, triglyceride and phospholipid. Cholesterol and glycerolipid synthesis in the liver were significantly reduced leading to a lower lipoprotein secretion rate in both normolipidemic and diet-induced hyperlipidemic rats.
Atherosclerosis 1988 Dec
PMID:Effects of ciprofibrate and fenofibrate on liver lipids and lipoprotein synthesis in normo- and hyperlipidemic rats. 324 Mar 33

(1) Rats were fed on diets enriched with sucrose, beef tallow or corn oil and treated for 11-16 days with 50 mg of benfluorex per kg of body weight. By these times the growth rate and food intake were not significantly different from those of control rats. (2) Benfluorex approximately halved the concentration of circulating triacylglycerol in rats fed the beef tallow or sucrose diets. (3) It did not significantly alter the total lipoprotein lipase activity in diaphragm, heart and adipose tissue. (4) The clearance of triacylglycerols from chylomicrons exhibited two t 1/2 values of about 0.6 and 6.9 min in rats fed the beef tallow diet. Benfluorex did not significantly alter these values. (5) Benfluorex did not significantly alter the rate of appearance of triacylglycerol in the blood of rats injected with Triton WR 1339 to block triacylglycerol uptake. It did, however, decrease the rise in circulating glucose which presumably resulted from the stress of the procedure. (6) Benfluorex decreased the extent and duration of the rise in serum corticosterone when rats maintained on the corn oil diet were fed acutely with fructose. It also decreased the circulating concentrations of glycerol, triacylglycerol and glucose after fructose feeding. (7) Rats fed on the corn oil diet and then treated with benfluorex had lower concentrations of circulating glucose, triacylglycerol, glycerol and fatty acids after being injected with 2-deoxyglucose. (8) It is proposed that some of the long-term hypoglycaemic and hypotriglyceridaemic effects of benfluorex could be mediated indirectly through changes in endocrine balance, perhaps via the serotonergic system and in particular, by decreasing the effects of stress hormones relative to insulin. The implications of these findings are discussed in relation to controlling metabolism in stress conditions and for the management of obesity, diabetes and atherosclerosis.
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PMID:Effects of chronic administration of benfluorex to rats on the metabolism of corticosterone, glucose, triacylglycerols, glycerol and fatty acid. 334 1

The lipid-lowering profile of ethyl 10,11-dihydro-4-methoxydibenz[b,f]-(1,4)oxazepine-8-carboxylate (AZ-1355) has been evaluated using clofibrate as a reference compound. This compound is structurally unrelated to any other hypolipidemic agent. AZ-1355 was selected not only for its effect in reducing serum lipids, but also because it inhibits platelet aggregation in vivo and elevates the prostaglandin I2/thromboxane A2 ratio in vitro. It lowers serum total cholesterol in Triton-treated hyperlipidemic mice, and also lowers serum total cholesterol and triglyceride in dietary hyperlipidemic rats. In golden hamsters chosen for further evaluation, AZ-1355 reduced serum, liver and cardiac lipids, improved the beta/alpha-lipoprotein ratio and increased the HDL cholesterol. Thus, it is apparent that the lipid-lowering profile of AZ-1355 differs from that of clofibrate.
Atherosclerosis
PMID:The lipid-lowering profile in rodents. AZ-1355, a new dibenzoxazepine derivative. 733 5

Since inhibitors of HMG-CoA reductase lower plasma triglycerides rather than cholesterol in rats, we compared the triglyceride-lowering activity of lovastatin in rats to that of atorvastatin, a more potent synthetic inhibitor, prior to evaluating these drugs in established animal models in which low density lipoproteins (LDL) rather than high density lipoproteins (HDL) are the major transporters of plasma cholesterol. Atorvastatin was more efficacious than lovastatin in normal, chow-fed rats, and more potent in rats with endogenous hypertriglyceridemia (sucrose-fed). In hypertriglyceridemic rats plasma apoB concentrations decreased only with atorvastatin (30 mg/kg), and VLDL-triglyceride secretion (Triton method) was also decreased more by atorvastatin. The inactive enantiomer of atorvastatin did not lower plasma triglycerides. Thus, triglyceride-lowering was dependent upon inhibition of HMG-CoA reductase. Liver unesterified cholesterol and cholesteryl esters (mg/g) were increased by both drugs in normal rats but remained unchanged in hypertriglyceridemic rats. In normal, chow-fed guinea pigs atorvastatin was a more potent cholesterol-lowering drug, and unlike lovastatin, lowered plasma triglycerides and VLDL-cholesterol. In casein-fed rabbits with endogenous hypercholesterolemia and in chow-fed rabbits atorvastatin lowered LDL-cholesterol more potently than lovastatin, but in chow-fed rabbits neither drug had an effect on the in vivo rate of VLDL-lipid secretion, suggesting that efficacy was due to inhibition of direct LDL production and/or enhanced LDL clearance. We conclude that normal rats can be used as a preclinical tool to assess the efficacy of HMG-CoA reductase inhibitors since triglyceride-lowering correlates with cholesterol-lowering in LDL animal models. In this regard atorvastatin is a more potent hypolipidemic agent than lovastatin in animals. A common but not sole mechanism for these drugs may be direct inhibition of the hepatic production of the major apoB-containing lipoprotein in a given species, e.g. VLDL in rats and LDL in guinea pigs and rabbits.
Atherosclerosis 1995 Oct
PMID:Lipid-lowering activity of atorvastatin and lovastatin in rodent species: triglyceride-lowering in rats correlates with efficacy in LDL animal models. 880 69

We examined the effect of long-term (6 months) hyperinsulinemia on VLDL-triglyceride turnover in male Wistar rats. Hyperinsulinemia was induced in rats by daily s.c. injection of Ultralente insulin (6 U/day at 19:00). Fructose (F) or glucose (G) was supplied in the drinking water (10%) in order to prevent hypoglycemia. The rats were divided into 5 groups: (1) hyperinsulinemia with F water: group F + I; (2) hyperinsulinemia with G water: group G + I; (3) F water alone: group F; (4) G water alone: group G; and (5) control rats without sugar water group C. After 6 months of daily insulin injection triglyceride secretion rate (TGSR) was estimated using Triton WR1339 in all the rats. Groups F + I and G + I were obese and hypoglycemic compared to the other groups. Fasting plasma glucose level of group F was higher than any other group value. TGSR of group F + I was significantly higher than that of the control group, while that of group G + I was not, indicating that long-term hyperinsulinemia can stimulate hepatic triglyceride production when the rats were supplemented only with fructose. On the other hand, the rats in group G + I showed the lowest plasma free fatty acid level of all and their postheparin lipolytic activity was significantly elevated compared to that of the control rats. Moreover, they had suppressed plasma triglyceride levels and its fractional catabolic rate was significantly increased, suggesting that hyperinsulinemia can still stimulate triglyceride removal from the circulation of glucose supplemented rats even at month 6. In conclusion, exogenous hyperinsulinemia can stimulate hepatic triglyceride secretion even after 6 months duration when supplemented with fructose, while its stimulating effect on triglyceride removal from the circulation can be seen only with glucose supplementation. Thus, the effect of long-term hyperinsulinemia on plasma triglyceride turnover differs depending on the supplemented monosaccharides.
Atherosclerosis 1997 Feb 28
PMID:Effect of long-term exogenous hyperinsulinemia and fructose or glucose supplementation on triglyceride turnover in rats. 906 14

Extraction of ECV304 endothelial cells in 1% Triton X-100 at 4 degrees C resulted in a detergent-insoluble pellet that contained 90% of the caveolin, 78% of the src family kinases and 99% of the annexin II. When detergent-treated cells were loaded beneath a 10-30% sucrose gradient the caveolin and a large proportion of the cellular cholesterol floated at a density of 1.09 g/cm3, characteristic of caveolae and glycosphingolipid-rich membranes. With extended centrifugation the src family kinases, which were initially associated with this floating material, sedimented to the bottom of the gradient. Annexin II remained on the bottom of the gradient under both centrifugation conditions. After 24-h incubation with oxidised low density lipoprotein (oxLDL) about 7.5% of the total sterol in the cells was replaced by 7-ketocholesterol, the major oxysterol found in oxLDL. The majority of this 7-ketocholesterol was found in the light membrane fraction on sucrose gradients. Under these conditions src kinase activity more than doubled in the Triton-resistant fraction, without changes in the concentration of src kinase protein. Introducing oxysterols directly into the medium bathing ECV304 cells for 1 h also modulated the activity of src family kinases in the detergent-resistant membranes. An elevation in activity was observed for 7-ketocholesterol while 7alpha-hydroxycholesterol, 7alpha-hydroxycholesterol and cholesterol epoxide all produced decreases in the background level of src kinase activity. We conclude that 7-ketocholesterol and possibly other components of oxLDL can equilibrate into glycosphingolipid-rich membranes and increase the activity of src kinases, possibly by interaction with caveolin.
Atherosclerosis 1999 Apr
PMID:Src family kinase activation in glycosphingolipid-rich membrane domains of endothelial cells treated with oxidised low density lipoprotein. 1021 69

The effects of diabetes and lipoprotein lipase (LpL) on plasma lipids were studied in mice expressing human apolipoprotein B (HuBTg). Our overall objective was to produce a diabetic mouse model in which the sole effects of blood glucose elevation on atherosclerosis could be assessed. Mice were made diabetic by intraperitoneal injection of streptozotocin, which led to a 2- to 2. 5-fold increase in plasma glucose. Lipids were assessed in mice on chow and on an atherogenic Western type diet (WTD), consisting of 21% (wt/wt) fat and 0.15% (wt/wt) cholesterol. Plasma triglyceride and cholesterol were the same in diabetic and non-diabetic mice on the chow diet. On the WTD, male diabetic HuBTg mice had a >50% increase in plasma cholesterol and more very low density lipoprotein (VLDL) cholesterol and triglyceride as assessed by FPLC analysis. A Triton study showed no increase in triglyceride or apolipoprotein B production, suggesting that the accumulation of VLDL was due to a decrease in lipoprotein clearance. Surprisingly, the VLDL increase in these mice was not due to a decrease in LpL activity in postheparin plasma. To test whether LpL overexpression would alter these diabetes-induced lipoprotein changes, HuBTg mice were crossed with mice expressing human LpL in muscle. LpL overexpression reduced plasma triglyceride, but not cholesterol, in male mice on WTD. Aortic root atherosclerosis assessed in 32-week-old mice on the WTD was not greater in diabetic mice. In summary, diabetes primarily increased plasma VLDL in HuBTg mice. LpL activity was not decreased in these animals. However, additional LpL expression eliminated the diabetic lipoprotein changes. These mice did not have more atherosclerosis with diabetes.
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PMID:Streptozotocin-induced diabetes in human apolipoprotein B transgenic mice. Effects on lipoproteins and atherosclerosis. 1058 44

Lipid disorders and cardiovascular diseases have been related in many studies. We here studied the influence of acute ingestion of a long chain triglyceride (LCT) emulsion (rich in triglycerides) on plasma triglyceride (TG) and total cholesterol (TC) levels in laboratory animals (Wistar rats), comparing it with the induction of hypertriglyceridaemia and hypercholesterolaemia by Triton WR-1339 injection. The results show that Triton would be suitable for inducing hypercholesterolaemia but not hypertriglyceridaemias similar to those in humans. The LCT emulsion intake, however, provoked transitory hyperlipaemia with values similar to those often found in hyperlipaemic subjects, and would thus be suitable for testing possible antilipaemic treatments. Our study also presents a model of hypertriglyceridaemia, hypercholesterolaemia and obesity in experimental animals, provoked by a chronic intake of an LCT emulsion. This model may be useful in investigating the mechanisms of the pathogenesis of atherosclerosis and the pharmacological treatment of obesity and dyslipaemias.
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PMID:Experimental hypertriglyceridaemia and hypercholesterolaemia in rats. 1075 70

Studies in humans have indicated that dietary salt restriction raises plasma levels of total cholesterol (TC) and triacylglycerols (TAG). In order to explain the mechanisms involved, a rat experimental model was developed consisting of chronic feeding ad libitum isocaloric diets with variable sodium chloride contents. Rates of synthesis of plasma TAG were measured either as the increase of plasma TAG after blocking its removal from plasma by the intra-arterial pulse infusion of Triton-WR 1339, or as the plasma rate of incorporation of [(14)C]-oleic acid [(14)C]-TAG. Plasma TAG removal rate was determined by the intra-arterial pulse infusion of a lipid emulsion. Severe salt restriction increased the plasma concentrations of TAG (71%) and of TC (10%). This result was not due to modification of the rate of synthesis of plasma TAG but was attributed to a 55% slower rate of removal of the TAG-containing lipoproteins. An increased plasma non-esterified fatty acid concentration, probably due to a salt restriction-related insulin resistance, may have impaired the activity of the enzyme lipoprotein lipase.
Atherosclerosis 2001 Sep
PMID:The rise of the plasma lipid concentration elicited by dietary sodium chloride restriction in Wistar rats is due to an impairment of the plasma triacylglycerol removal rate. 1150 Jan 77

The effects of ip administration of NSAIDs in experimentally induced hyperlipidemia in rats was studied. An isotonic solution of Triton WR1339 (tyloxapol) was administered ip to rats one hour after ip administration of the examined anti-inflammatory drug. After 24 h, blood was collected for the determination of plasma total cholesterol (TC), LDL and trigluceride (TG) concentrations. The NSAIDs used in our experimental model are selective or non selective COX-1 inhibitors as well as one non selective COX-2 inhibitor. Most of the drugs significantly reduced the TC, TG and LDL concentrations in the plasma of hyperlipidemic rats. While studies link atheromatosis to inflammation, our results potentially also link anti-inflammatory activity with hypolipidemia. Thus, NSAIDs not only may address the inflammatory aspect of atherosclerosis but also may contribute directly by inducing hypolipidemia.
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PMID:Experimental hyperlipidemia and the effect of NSAIDs. 1223 Dec 15


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