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)

In 17 patients with primary mixed hyperlipidemia we studied levels and composition of lipoproteins in fasting plasma, lipoprotein-modifying enzymes, and postprandial lipoprotein metabolism after an oral fat-tolerance test supplemented with vitamin A before, and 12 weeks after treatment with etophylline clofibrate. With treatment, fasting plasma cholesterol, triglycerides, and the levels of very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL) decreased significantly; high density lipoprotein (HDL) cholesterol increased significantly. Treatment caused also an increase in the protein content of IDL, a decrease in the triglyceride content of LDL, and an increase in the size of LDL as assessed by gradient gel electrophoresis. Concentrations of triglycerides, chylomicrons, and chylomicron remnants after an oral fat load supplemented with vitamin A decreased by 33%, 30% and 6%, respectively (P < 0.005; P < 0.01; and P < 0.05). The activity of lipoprotein lipase and hepatic lipase in postheparin plasma increased by 51% and 45%, respectively (P < 0.01; P < 0.05). We found a decrease in the mass concentration of cholesteryl ester transfer protein (P < 0.05). Stepwise multiple regression analysis showed that the triglyceride content of LDL is determined primarily by fasting triglycerides (r = + 0.53, P < 0.05;baseline) and cholesteryl ester transfer protein (r = + 0.49, P < 0.05; 12 weeks); in contrast, the triglyceride content of HDL3 is determined exclusively by accumulation of postprandial triglycerides (r = + 0.67; P < 0.05; baseline) and postprandial chylomicrons (r = +0.87; P < 0.005; 12 weeks). We conclude that hypolipidemic treatment with etophylline clofibrate favorably affects the cardiovascular risk factor profile in primary mixed hyperlipidemia.
Atherosclerosis 1995 Oct
PMID:Treatment of primary mixed hyperlipidemia with etophylline clofibrate: effects on lipoprotein-modifying enzymes, postprandial lipoprotein metabolism, and lipoprotein distribution and composition. 880 71

Increased concentration of cholesteryl ester transfer protein (CETP) in plasma favours a lipoprotein profile characterized by a reduced high density lipoprotein (HDL) cholesterol. Previous studies have demonstrated that a diet high in cholesterol and saturated fat (HCSF) is associated with elevated plasma CETP and increased release of cholesterol ester transfer activity (CETA) from hamster adipose tissue incubated in vitro. The present study investigated the effects of vitamin E (Vit.E) ingestion on plasma CETP activity and adipose tissue CETA in Syrian Golden hamsters. A regular diet supplemented by the addition of 1% cholesterol and 10% coconut oil (w/w) was associated with a time-dependent increase in plasma CETP activity and increased release of adipose CETA following incubation of fragments of perirenal adipose tissue. Vit.E ingestion (100 mg/kg body weight per day for 8 weeks) suppressed 85% of the increase of CETA released from cultured hamster adipose tissue and 70% of the increase of plasma CETP activity induced by the HCSF diet. Significant decreases in plasma total and LDL cholesterol and an increase in HDL cholesterol were found in hamsters receiving the HCSF diet plus Vit.E compared to the animals on the HCSF diet alone. In the hamsters on regular chow, Vit.E ingestion alone did not significantly alter adipose tissue CETA, plasma CETP activity or plasma lipoproteins. The results indicate that Vit.E prevents the HCSF diet-induced increase in plasma CETP activity, probably via a reduction of CETA secretion from hamster adipose tissue. This suggests that Vit.E supplementation may help to ameliorate the dyslipidemia caused by a HCSF diet through its inhibitory influence on CETP production in adipose tissue.
Atherosclerosis 1996 Aug 02
PMID:Effect of dietary vitamin E supplements on cholesteryl ester transfer activity in hamster adipose tissue. 883 Sep 34

The exon 16 of the cholesteryl ester transfer protein (CETP) gene was screened for possible mutations in patients with low plasma high-density lipoprotein cholesterol (HDL-C) levels and established coronary heart disease. 115 men who had undergone coronary bypass surgery were compared with a random population sample of 515 subjects. A single G to A substitution at base pair 1696 was found in the 3' untranslated region of the CETP gene. Among the patients with low HDL-C, the plasma CETP activity was 29% lower (P = 0.002) in the subjects homozygous for the mutation than in those with other genotypes. The same effect was observed in the random population sample (P = 0.02). The mutation did not affect the plasma lipid or lipoprotein values, although the mean HDL-C tended to be slightly higher and the ratio of cholesterol content in the apo B-containing lipoproteins to HDL-C slightly lower in the homozygotes compared with the other genotypes. In conclusion, we describe a prevalent mutation at the CETP gene locus associated with low plasma CETP activity. Our results support previous findings suggesting that the genes in chromosome 16 may be important in the regulation of reverse cholesterol transport and in protection against coronary heart disease.
Atherosclerosis 1996 Aug 02
PMID:A polymorphic site in the 3' untranslated region of the cholesteryl ester transfer protein (CETP) gene is associated with low CETP activity. 883 Sep 36

Abnormalities in cholesteryl ester transfers may play a role in the development of atherosclerosis observed in patients with end-stage renal failure treated by chronic hemodialysis. Net neutral-lipid transfers and cholesteryl ester transfer protein activity and mass were investigated in 20 hemodialyzed patients, arbitrarily divided into two groups based on fasting triglyceride levels, and compared to triglyceride-matched control groups. In the hypertriglyceridemic subjects (plasma triglyceride values > 150 mg/dl), high-density lipoprotein cholesterol was decreased, and the net cholesteryl ester transfer rates were significantly higher than the rates in normolipidemic subjects. The comparison of subjects matched for plasma triglyceride and cholesterol levels showed no significant difference in cholesteryl ester or triglyceride transfer rates between patients and controls. Our results suggest that normal or elevated net neutral-lipid transfers are not related to the renal status of the subjects, but rather to their plasma triglyceride levels.
 ...
PMID:Neutral-lipid transfers and cholesteryl ester transfer protein in hemodialyzed patients. 888 76

Hypercholesterolemic women (n = 19) sequentially maintained on a long-term saturated (SAT) or a polyunsaturated (PUFA) fatty acid-rich diet, respectively, were studied in the fasting state and after a meal rich in SAT or PUFA. When apo B-containing lipoprotein was excluded from plasma the in vitro HDL-14C-cholesterol esterification rate was identical for the saturated (SAT) and polyunsaturated (PUFA) fatty acid diets, and did not increase during the postprandial period. Rates of transfer of 14C-cholesteryl ester to apo B-containing lipoproteins from HDL were also similar for both diets in the fasting state and increased to the same extent in the postprandial period in parallel with the rise in plasma triglycerides. When transfer data were related to the plasma concentration of apo B, the gain of cholesteryl ester by the triglyceride-containing particles (VLDL + LDL) also increased in the postprandial period to a similar extent for both diets. Cholesteryl ester transfer protein (CETP) concentration measured by radioimmunoassay was similar during both experimental diets, although greater in the postprandial period for the PUFA diet. The rate limiting factor for CETP-mediated transfer of HDL-derived cholesteryl ester (CE) was the plasma triglyceride concentration, that is, the content of triglycerides per lipoprotein particle and the quantity of TG-containing particles (VLDL + LDL). In contrast, the fatty acid composition of these particles had less effect on CETP-mediated CE transfer.
Atherosclerosis 1996 Oct 25
PMID:Plasma cholesteryl ester synthesis, cholesteryl ester transfer protein concentration and activity in hypercholesterolemic women: effects of the degree of saturation of dietary fatty acids in the fasting and postprandial states. 890 52

Transfers or exchanges of cholesterol esters and triglycerides between lipoproteins are mediated by a specialized protein referred to as cholesteryl ester transfer protein (CETP), whereas those of phospholipids (PLs) are facilitated by both CETP and a specific phospholipid transfer protein (PLTP). In the present study, the authors compared phospholipid transfer (PLT) in normal subjects and in patients with non-insulin-dependent diabetes (NIDD), which is associated with an increased risk of atherosclerosis. PLT was measured in different recombination experiments using an isotopic assay in which the transfer of labelled PLs from very low-density lipoprotein (VLDLs) and low-density lipoproteins (LDLs) to high-density lipoproteins (HDLs) was determined. This allowed discrimination between the roles of VLDLs + LDLs, HDLs, and plasma PLT activity (PLTA). VLDL + LDL-dependent PLT, HDL-dependent PLT and PLTA were decreased in NIDD. VLDL + LDL-dependent PLT was found to be negatively correlated with the PL/apolipoprotein B ratio, whereas HDL-dependent PLT was positively correlated with the HDL2/HDL3 and PL/apolipoprotein A-I ratios and negatively correlated with the flow activation energy at the HDL surface. The HDL2/HDL3 ratio was positively correlated with PLTA but not with CETP, which confirms previous reports suggesting that PLTP might act as an HDL conversion factor. These data show that several abnormalities in PLT occur in NIDD and raise the question as to whether a lowered PLT might be a new characteristic of dis factors associated with an increased risk of atherosclerosis.
 ...
PMID:Multiple abnormalities in the transfer of phospholipids from VLDL and LDL to HDL in non-insulin-dependent diabetes. 890 50

The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high-density lipoproteins (HDL) into very-low-density lipoproteins (VLDL) with a reciprocal exchange of triglycerides. Plasma CETP is mainly bound to HDL and is involved in the interconversion of these lipoproteins. In experimental models such as transgenic mice, CETP activity decreases HDL cholesterol and increases the cholesteryl ester content of apo B-containing lipoproteins. In humans, CETP activity and concentration are positively correlated with VLDL-LDL cholesterol. Clinical studies suggest that the effect of CETP on HDL cholesterol depends on the amount of acceptor lipoproteins. CETP activity is negatively correlated with HDL cholesterol only in hypertriglyceridemic states. Various CETP gene mutations have been reported, they induce hyper-alpha-lipoproteinemia. On the other hand, the impact of the variability of CETP gene on HDL cholesterol variations in Caucasians is controversial. CETP is often involved in secondary dyslipidemia and is susceptible to modify the composition of plasma lipoproteins in an atherogenic way. The real impact of CETP activity on atherosclerosis is still unknown. CETP is susceptible to play a proatherogenic role since it mediates a redistribution of plasma cholesterol from lipoproteins associated with a protection against atherosclerosis into the proatherogenic apo B-containing lipoproteins. However, CETP mediates one of the steps of the reverse cholesterol transport, an antiatherogenic process that channels cholesterol from peripheral tissues back to the liver.
 ...
PMID:Cholesteryl ester transfer protein: an enigmatic protein. 896 91

Rates of ester formation from [3H]cholesterol and of [3H]cholesteryl ester transfer from the HDL-containing plasma fraction to lipoproteins of lighter densities (apo B-containing LP) and plasma cholesteryl ester transfer protein concentration (CETP) were measured in normotriglyceridemic Type II diabetics (n = 11) and normal controls (n = 10) both in the fasting state and 4 h after a standard milk-shake test meal (50g of fat/m of body surface). The percent of [3H]cholesteryl ester synthesis was measured in a plasma [3H]cholesterol-HDL containing preparation incubated for 30 min and the [3H]cholesteryl ester transfer was measured upon precipitation of apo B-containing lipoproteins with dextran sulphate/MgCl2 following a 2 h period of plasma incubation with [3H]cholesteryl ester-HDL. The test meal significantly increased the plasma triglyceride concentration and to a similar extent in diabetics and in normal controls. Both a HDL-[3H]cholesteryl ester synthesis and transfer rates were equally stimulated in diabetics and in controls. When data were expressed by the concentration of plasma triglycerides, cholesteryl ester formation and transfer rates were similar in the alimentary and fasting periods, and when expressed per apo B concentration, cholesteryl ester transfer rates rose during the alimentary period in both diabetics and controls indicating that there was a net gain of cholesteryl ester per apo B lipoprotein. Plasma CETP mass, and neutral lipid transfer activity were similar in diabetics and normal controls demonstrating that the reverse transport of cholesterol through the apo B lipoprotein pathway is not altered in normotriglyceridemic Type II diabetics.
Atherosclerosis 1996 Nov 15
PMID:Plasma cholesteryl ester transfer protein concentration, high-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins in the fasting state and after a test meal are similar in Type II diabetics and normal controls. 900 8

Malondialdehyde-modified LDL(MDA-LDL) is one of the major oxidative LDL. MDA-LDL was determined by enzyme immunoassay in patients with complete and partial cholesteryl ester transfer protein(CETP) deficiency. Significantly increased serum MDA-LDL levels and MDA-LDL/apoB ratios in the LDL fraction were observed in patients with complete CETP deficiency but not for those with partial CETP deficiency. The present results may indicate that patients with complete CETP deficiency have a higher risk for atherosclerosis than those with partial CETP deficiency and normal.
 ...
PMID:[Complete cholesteryl ester transfer protein deficiency increases oxidized-LDL in plasma]. 902 43

Although the relationship between the actions of cholesteryl ester transfer protein (CETP) and atherosclerosis is complex, a strong body of evidence suggests that its activity (cholesteryl ester transfer [CET]) is proatherogenic. We have previously shown that CET is increased in IDDM patients receiving conventional subcutaneous insulin treatment and normalized when systemic insulin levels are lowered with intraperitoneal insulin delivery (IP). Since CET has been found by many observers to also be accelerated in NIDDM, we sought to determine whether the same salutary effect could be achieved in insulin-requiring NIDDM men before and 7 months after randomization to an intensive treatment regimen (Rx) of either IP (n = 9) or multiple daily insulin injections (MDI; n = 13). HbA1c improved to the same degree in both groups (MDI group: 9.4 +/- 1.1% pre-Rx vs. 7.2 +/- 0.7% post-Rx [P < 0.001]; IP group: 9.2 +/- 1.3% pre-Rx vs. 7.1 +/- 0.5% post-Rx [P < 0.001]). Compared with pre-Rx levels, plasma triglycerides were not significantly changed by either treatment (MDI group: 136 +/- 80 mg/dl pre-Rx vs. 139 +/- 87 mg/dl post-Rx; IP group: 157 +/- 63 mg/dl pre-Rx vs. 188 +/- 89 mg/dl post-Rx), though an upward trend followed IP. Before randomization, CET estimated with both mass and isotopic assays was greater in the NIDDM subjects than in nondiabetic control subjects (P < 0.001). With improved glycemic control, CE mass transfer declined in both groups, but only reached normal levels in the IP group (MDI group at 2 h: 49.0 +/- 13.7 [mean +/- SD] pg pre-Rx vs. 29.5 +/- 15.3 microg post-Rx [-39.7%, P < 0.01]; IP group at 2 h: 40.8 +/- 23.3 microg pre-Rx vs. 10.9 +/- 6.5 microg post-Rx [-73.2%, P < 0.05]) and remained abnormally increased (P < 0.005) in the subjects receiving MDI. Total lipolytic activity after intensive treatment was unchanged from pretreatment levels, which were similar to those of the reference group. Although directional changes in lipoprotein lipase (LpL) and hepatic triglyceride lipase (HTGL) similar to those found in IDDM after MDI and IP were observed, they were not statistically significant. Thus, while improved glycemic control alone achieved by either MDI or IP reduced the pathological increase in CET in these insulin-treated NIDDM men, normalization was only achieved in those treated with IP. Despite near-normal HbA1c levels, CET remained abnormally increased in NIDDM patients treated rigorously with conventional subcutaneous insulin delivery.
 ...
PMID:Effects of multiple daily insulin injections and intraperitoneal insulin therapy on cholesteryl ester transfer and lipoprotein lipase activities in NIDDM. 903 97


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