UMLS:C0042373 - FACTA Search

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Query: UMLS:C0042373 (vascular disease)
17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Variation of HDL cholesterol levels in man shows a strong inverse relationship to the incidence of atherosclerotic vascular disease. Thus the regulation of HDL cholesterol levels has been the subject of intense investigation. Human genetic differences in cholesteryl ester transfer protein and hepatic lipase illustrate the importance of these factors in the normal catabolism of HDL, while metabolic and population studies show that lipoprotein lipase activity plays a central role in the transfer of lipids and apoproteins into HDL. Metabolic turnover studies in humans suggest that variations in the fractional catabolism of the HDL structural proteins, apoA-I and apoA-II, account for much of the variation of HDL levels in human populations. Although the catabolism of these apolipoproteins is poorly understood, changes in the core lipid composition of HDL may lead to changes in catabolism of the HDL proteins. The core lipid composition of HDL appears to be determined by lipid transfer processes, and the activities of lipoprotein and hepatic lipase. Thus many genetic and environmental factors that influence HDL levels appear to operate by changing the activities of the lipases or the lipid transfer process.
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PMID:Metabolic and genetic control of HDL cholesterol levels. 161 89

Cholesteryl ester transfer from solid-phase bound HDL to endogenous plasma HDL or VLDL/LDL was determined in 50 patients with primary disorders of lipid metabolism and 27 normolipidemic subjects. Transfer to the plasma HDL pool was significantly reduced in familial hypercholesterolemia, familial combined hyperlipidemia, hypoalphalipoproteinemia and dysbetalipoproteinemia. Subfractionation of HDL revealed that the lipid transfer to HDL3 was significantly reduced in all patient groups while transfer to HDL2 was increased in those with dysbetalipoproteinemia and familial hypertriglyceridemia. Transfer to LDL and VLDL was increased only in patients with dysbetalipoproteinemia and hypoalphalipoproteinemia. Reduced transfer to HDL occurred in samples with altered HDL composition; particularly where HDL-triglyceride was significantly increased and HDL-cholesteryl esters were reduced. Transfer of cholesteryl ester to HDL3 was significantly decreased in patients with vascular disease. These findings indicate that impaired interaction of cholesteryl ester transfer protein with the HDL3 pool may contribute to the risk of coronary heart disease in patients with specific plasma lipid abnormalities.
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PMID:Relationship between cholesteryl ester transfer activity and high density lipoprotein composition in hyperlipidemic patients. 275 50

The effect of variation at the cholesteryl ester transfer protein (CETP) gene locus and in the apolipoprotein (apo) AI-CIII-AIV gene cluster on the susceptibility of individuals with non-insulin-dependent diabetes mellitus (NIDDM) to atherosclerotic vascular disease was studied in 136 male and 122 female patients with NIDDM. The prevalence of myocardial infarction was high (38%) in patients with the EcoNI genotype 2-2 of the CETP gene locus (= 2-2; subjects homozygous for the absence of the restriction site) compared with patients with the genotype 1-1 (= 1-1; subjects homozygous for the presence of the restriction site) (18%, p < 0.02). The prevalence of any evidence of coronary heart disease (CHD) (presence of ischaemic ECG changes or definite myocardial infarction) was high in 2-2 (73%) compared with the genotype 1-2 (= 1-2; heterozygous for the presence of the restriction site) (52%, p < 0.02) and genotype 1-1 (p = 0.06). CHD was more prevalent in men with 2-2 (70%) than in those with 1-1 (42%, p < 0.05), but in women no significant differences were found in the prevalences of CHD between the EcoNI genotypes. Neuropathy was more often present in the patients with 2-2 (31%) than in those with 1-1 (12%, p < 0.02) or 1-2 (14%, p < 0.01). Plasma total cholesterol and total- and VLDL-triglycerides were higher in women with the EcoNI genotype 1-1 than in those with the genotype 1-2. In men no significant differences in plasma lipids were found. In addition, the prevalence of cerebrovascular disease was high (21%) in the patients with the genotype 1-1 of the TaqIB polymorphism compared with the genotype 2-2 (6%, p < 0.02). None of the alleles defined by four polymorphisms in the apo AI-CIII-AIV gene region were associated with an increased risk for macroangiopathy. The PstI polymorphism had an effect on plasma triglyceride levels. At the CETP locus one pair of loci (TaqIB and EcoNI) and three pairs of loci at the apo AI-CIII-AIV gene cluster (SacI and MspI, SacI and PvuII and MspI and PvuII) showed significant allelic association. In conclusion, the variation of CETP locus modulates the risk for diabetic complications in patients with NIDDM and the effect seems to be different between men and women. In contrast, the AI-CIII-AIV gene cluster polymorphisms seem not to be related to the risk of CHD in NIDDM.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:DNA polymorphisms at the locus for human cholesteryl ester transfer protein (CETP) are associated with macro- and microangiopathy in non-insulin-dependent diabetes mellitus. 782 Sep 35

Among patients undergoing maintenance hemodialysis, a decreased high-density lipoprotein cholesterol (HDL-C) concentration is among the most common abnormalities of lipid metabolism and apparently is an independent risk factor for vascular disease. A common missense mutation of cholesteryl ester transfer protein gene, D442G (Asp 442 to Gly), increases HDL-C levels through the reduced activity of cholesteryl ester transfer from HDL to VLDL, but the mutation also may lead to reduced activity of reverse cholesterol transport. To investigate the effect of the D442G polymorphism on atherosclerotic complications in dialysis patients, the genotype and allele frequency of the polymorphism were determined in 414 unselected dialysis patients and 220 control subjects, and postprandial serum lipid levels were measured in the dialysis patients. A similar genotype distribution was found between hemodialysis patients and healthy control subjects, and in dialysis patients with and without vascular disease. Serum levels of total cholesterol and HDL-C did not differ between patients with and without the mutation and in patients with and without vascular disease. However, patients with sub-median HDL-C levels (<45 mg/dl) had an independent odds ratio of 1.8 for vascular disease (95% confidence interval, 1.04 to 3.2; P < 0.05). In this low-HDL-C subgroup, patients with the D442G mutation had a significantly higher prevalence of vascular disease than those with no mutation (54.5% versus 24.4%; P < 0.05), and an independent odds ratio of 4.9 (95% confidence interval, 1.05 to 22.65; P < 0.05). In conclusion, the D442G mutation is an independent risk factor for atherosclerotic complications in dialysis patients with HDL-C levels below 45 mg/dl.
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PMID:A cholesteryl ester transfer protein gene mutation and vascular disease in dialysis patients. 1021 28

The new therapeutic options available to clinicians treating dyslipidaemia in the last decade have enabled effective treatment for many patients. The development of the HMG-CoA reductase inhibitors (statins) have been a major advance in that they possess multiple pharmacological effects (pleiotropic effects) resulting in potent reductions of low density lipoproteins (LDL) and prevention of the atherosclerotic process. More recently, the newer fibric acid derivatives have also reduced LDL to levels comparable to those achieved with statins, have reduced triglycerides, and gemfibrozil has been shown to increase high density lipoprotein (HDL) levels. Nicotinic acid has been made tolerable with sustained-release formulations, and is still considered an excellent choice in elevating HDL cholesterol and is potentially effective in reducing lipoprotein(a) [Lp(a)] levels, an emerging risk factor for coronary heart disease (CHD). Furthermore, recent studies have reported positive lipid-lowering effects from estrogen and/or progestogen in postmenopausal women but there are still conflicting reports on the use of these agents in dyslipidaemia and in females at risk for CHD. In addition to lowering lipid levels, these antihyperlipidaemic agents may have directly or indirectly targeted thrombogenic, fibrinolytic and atherosclerotic processes which may have been unaccounted for in their overall success in clinical trials. Although LDL cholesterol is still the major target for therapy, it is likely that over the next several years other lipid/lipoprotein and nonlipid parameters will become more generally accepted targets for specific therapeutic interventions. Some important emerging lipid/lipoprotein parameters that have been associated with CHD include elevated triglyceride, oxidised LDL cholesterol and Lp(a) levels, and low HDL levels. The nonlipid parameters include elevated homocysteine and fibrinogen, and decreased endothelial-derived nitric oxide production. Among the new investigational agents are inhibitors of squalene synthetase, acylCoA: cholesterol acyltransferase, cholesteryl ester transfer protein, monocyte-macrophages and LDL cholesterol oxidation. Future applications may include thyromimetic therapy, cholesterol vaccination, somatic gene therapy, and recombinant proteins, in particular, apolipoproteins A-I and E. Non-LDL-related targets such as peroxisome proliferator-activating receptors, matrix metalloproteinases and scavenger receptor class B type I may also have clinical significance in the treatment of atherosclerosis in the near future. Before lipid-lowering therapy, dietary and lifestyle modification is and should be the first therapeutic intervention in the management of dyslipidaemia. Although current recommendations from the US and Europe are slightly different, adherence to these recommendations is essential to lower the risk of atherosclerotic vascular disease, more specifically CHD. New guidelines that are expected in the near future will encompass global opinions from the expert scientific community addressing the issue of target LDL goal (aggressive versus moderate lowering) and the application of therapy for newer emerging CHD risk factors.
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PMID:Current, new and future treatments in dyslipidaemia and atherosclerosis. 1092 30

Cholesteryl ester transfer protein (CETP) may promote reverse cholesterol transport. An elevated concentration of high-density lipoprotein cholesterol (HDL-C) is a protective factor against atherosclerosis. However, the effects of CETP itself and its interaction with HDL-C have not been investigated in hemodialysis patients, who are at high risk for atherosclerosis and generally considered to have decreased reverse cholesterol transport. We investigated the independent or synergistic influence of postprandial serum CETP and HDL-C concentrations on apparent atherosclerotic complications in 202 hemodialysis patients aged 40 to 80 years. Patients with vascular disease (n = 39) had significantly lower concentrations of CETP than those without vascular disease (n = 163). When all study subjects were divided into four groups according to CETP and HDL-C concentrations based on median values, we found significant differences in the prevalence of vascular disease (test for trend, P < 0.005): 28.8% in group I (HDL-C < 48 mg/dL; CETP < 2.2 microgram/mL); 25.0% in group II (HDL-C < 48 mg/dL; CETP >/= 2.2 microgram/mL); 17.8% in group III (HDL-C >/= 48 mg/dL; CETP < 2.2 microgram/mL); and 6.9% in group IV (HDL-C >/= 48 mg/dL; CETP >/= 2.2 microgram/mL). Multiple logistic regression analysis retained the interaction term between HDL-C (in milligrams per deciliter) and CETP (in micrograms per milliliter), but not HDL-C or CETP itself, as inversely associated with vascular disease in the entire patient group. In patients with HDL-C levels at the median value or greater, CETP had an independent odds ratio of 0.31 (95% confidence interval, 0.1 to 0.97; P < 0.05) after adjusting for age. These results suggest that CETP may serve as a protective factor against vascular disease in hemodialysis patients, especially those with normal or elevated HDL-C concentrations.
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PMID:Cholesteryl ester transfer protein as a protective factor against vascular disease in hemodialysis patients. 1143 Nov 84

Cholesteryl ester transfer protein (CETP) is a key regulating factor of lipid metabolism, and the polymorphism of its gene may therefore be a candidate for modulating the lipid parameters, altering the susceptibility to atherosclerosis in type 2 diabetic subjects. In a group of 443 unrelated Japanese patients with type 2 diabetes, we studied the B1B2 polymorphism at the CETP locus, which is detectable with the restriction enzyme TaqI. Patients were separated into three groups according to genotype and compared based on their clinical characteristics, lipid parameters, and macrovascular complications. The B2 allele was associated in a dose-dependent fashion with higher HDL cholesterol and apolipoprotein AI levels, together with lower CETP concentrations. Furthermore, the prevalence of macrovascular complications, such as coronary heart disease, arteriosclerosis obliterans, and cerebral vascular disease, was significantly higher in subjects with the B1B1 genotype. Multiple logistic regression analysis also showed that the B1 allele of CETP genotype was associated with the incidence of these three complications independently of other risk factors. Thus, in type 2 diabetic patients, the B1B2 polymorphism of CETP gene is likely to be a strong genetic predictor of macrovascular complications.
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PMID:Relationship between TaqIB cholesteryl ester transfer protein gene polymorphism and macrovascular complications in Japanese patients with type 2 diabetes. 1187 95

Hemodialysis (HD) patients have a high mortality rate due to vascular disease (VD). Therefore, we investigated the effect of uremic dyslipidemia on VD in HD patients, with special consideration of the reverse cholesterol transport (RCT) system including high-density-lipoprotein cholesterol (HDL-C), cholesteryl ester transfer protein (CETP) and its genetic (D442G) mutation. In 414 HD patients, a sub-median HDL-C level (< 48 mg/dl) was an independent risk factor for VD. In the lower HDL-C status, the CETP mutation leading to CETP levels was independently associated with VD. In 210 selected patients, the CETP level was an independent protective factor against VD among those with higher HDL-C levels (> 45 mg/dl). We also measured serum homocysteine (Hcy) levels and examined its association with VD considering that hyperhomocysteinemia is a newly identified risk factor for atheroma. HD Patients (n = 545) had about 3 times the Hcy levels of the general population. A common C677T mutation in the gene of methylenetetrahydrofolate reductase (MTHFR) involved in Hcy metabolism was independently and directly related to serum Hcy levels with TT genotype patients having the highest levels. Patients with the TT genotype were younger and had a shorter duration of dialysis than those with the CT or CC genotype after adjustment for age at the initiation of dialysis, although there was no difference in VD prevalence among the genotypes and no association between Hcy levels and VD prevalence. In conclusion, lower HDL-C and CETP status was a risk factor for VD in HD patients, suggesting the importance of RCT. Serum Hcy levels were markedly increased in HD patients and the TT genotype may be associated with higher mortality. However, a large-scale prospective study is required to clarify whether hyperhomocysteinemia or the TT genotype is a VD risk factor among HD patients.
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PMID:[Risk factors for atherosclerotic vascular disease in patients on maintenance hemodialysis--with especial respect to reverse cholesterol transport system and hyperhomocysteinemia]. 1237 16

High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease (ASCVD), leading to the concept that pharmacologic therapy to raise HDL cholesterol levels may reduce ASCVD risk. There is substantial interest in the concept of inhibition of the cholesteryl ester transfer protein (CETP) as a novel strategy for raising HDL cholesterol levels, as well as reducing levels of atherogenic lipoproteins. This article reviews the physiology of CETP in lipoprotein metabolism and the data in animals and humans that are relevant to the question of whether CETP inhibition may some day be part of the clinical armamentarium for treating dyslipidemia and atherosclerotic vascular disease.
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PMID:Inhibition of cholesteryl ester transfer protein activity: a new therapeutic approach to raising high-density lipoprotein. 1529 7

Cholesteryl ester transfer protein (CETP) is a plasma enzyme that can modulate the profile of lipoproteins and is thus considered: 1) a mediator of vascular disease; and 2) a therapeutic target for vascular disease. In the present study, we pursued a better understanding of the effect of type 2 diabetes on the expression of CETP in obese patients. Obesity was accompanied by a 20% elevation in plasma CETP that was eliminated with the development of diabetes. These differences were observed for both men and women and were due to variations in the amount of CETP protein in the plasma. The mRNA and protein of both the full-length (CETPFL) and alternatively spliced (CETPDelta9) forms of CETP were lower in the liver, but not in either sc or omental adipose tissue depots, of diabetic obese subjects. Sterol response element binding proteins 1 and 2 were also lower in liver homogenates, suggesting that these transcription factors may mediate the effects of type 2 diabetes on hepatic CETP expression. Thus, the suppressive effects of type 2 diabetes in obese subjects are observed in both men and women and may be due, at least in part, to a suppression of hepatic CETP expression.
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PMID:Suppression of hepatic cholesteryl ester transfer protein expression in obese humans with the development of type 2 diabetes mellitus. 1564 3

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