UMLS:C0242339 - FACTA Search

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Query: UMLS:C0242339 (dyslipidemia)
13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV infection is associated with disturbances in lipid metabolism due to a host's response mechanism and the current antiretroviral therapy. The pathological appearance and progression of atherosclerosis is dependent on the presence of injurious agents in the vascular endothelium and variations in different subsets of candidate genes. Therefore, the Hha I polymorphism in the apolipoprotein E gene was evaluated in addition to triglycerides, total cholesterol, very low-density lipoprotein (VLDL), LDL, high-density lipoprotein (HDL), and apolipoprotein (apo) Al, B and E levels in 86 Brazilian HIV-infected patients and 29 healthy controls. The allele frequency for apoE in the HIV-infected group and controls was in agreement with data on the Brazilian population. Dyslipidemia was observed in the HIV group and verified by increased levels of triglycerides, VLDL and apoE, and decreased levels of HDL and apoAl. The greatest abnormalities in these biochemical variables were shown in the HIV-infected individuals whose immune function was more compromised. The effect of the genetic variation at the APOE gene on biochemical variables was more pronounced in the HIV-infected individuals who carried the apoE2/3 genotype. The highly active anti-retroviral therapy (HAART)-receiving group presented increased levels of total cholesterol and apoE. Dyslipidemia was a predictable consequence of HIV infection and the protease inhibitors intensified the increase in apoE values.
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PMID:Abnormalities in apolipoprotein and lipid levels in an HIV-infected Brazilian population under different treatment profiles: the relevance of apolipoprotein E genotypes and immunological status. 1520 89

Recent findings suggest that hypertension, dyslipidemia, diabetes mellitus, coronary heart disease are more common in adults who born with intrauterine growth restriction (IUGR). Several studies have shown that polymorphisms in angiotensin-converting enzyme (ACE) and apolipoprotein-E (Apo-E) are effective in developing the insulin resistance and also in increasing the risk of coronary heart disease. In present study, the frequencies of ACE, Apo-E gene polymorphisms, apolipoprotein-B (Apo-B) mutation and lipid compositions were determined in full-term newborn infants with IUGR. Forty-four newborn infants who had completed 36 weeks of gestational age, 24 healthy infants and 20 with IUGR, were taken into the scope of the study. While total cholesterol (TC) and Apo-B concentrations in infants with IUGR was found to be significantly higher than that of the control group (p<0.05), triglyceride (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL) and Apo-A1 levels were similar (p>0.05). An insertion/deletion (I/D) polymorphism with a significantly increased frequency was observed in the IUGR group (65%) as compared with the control group (33%) (p<0.05). When the distribution of the Apo-E gene polymorphism (E2, E3 and E4) was studied, no difference was found between the IUGR and control groups with respect to frequency. No Apo-B gene mutation was identified in the study groups. In conclusion, we may suggest that I/D polymorphism is responsible, though in part, for the etiology of intrauterine growth restriction. Levels of total cholesterol and Apo-B are elevated in IUGR infants, suggesting a linkage between low birth weight and atherosclerosis.
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PMID:The role of angiotensin-converting enzyme and apolipoprotein-E gene polymorphisms on lipid compositions in newborn infants with intrauterine growth restriction. 1522 14

Hypertriglyceridemia is a common pathological condition in humans of mostly unknown etiology. Here we report induction of dyslipidemia characterized by severe hypertriglyceridemia as a result of point mutations in human apolipoprotein A-I (apoA-I). Adenovirus-mediated gene transfer in apoA-I-deficient (apoA-I(-)(/)(-)) mice showed that mice expressing an apoA-I[E110A/E111A] mutant had comparable hepatic mRNA levels with WT controls but greatly increased plasma triglyceride and elevated plasma cholesterol levels. In addition, they had decreased apoE and apoCII levels and increased apoB48 levels in very low-density lipoprotein (VLDL)/intermediate-density lipoprotein (IDL). Fast protein liquid chromatography (FPLC) analysis of plasma showed that most of cholesterol and approximately 15% of the mutant apoA-I were distributed in the VLDL and IDL regions and all the triglycerides in the VLDL region. Hypertriglyceridemia was corrected by coinfection of mice with recombinant adenoviruses expressing the mutant apoA-I and human lipoprotein lipase. Physicochemical studies indicated that the apoA-I mutation decreased the alpha-helical content, the stability, and the unfolding cooperativity of both lipid-free and lipid-bound apoA-I. In vitro functional analyses showed that reconstituted HDL (rHDL) particles containing the mutant apoA-I had 53% of scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux capacity and 37% capacity to activate lecithin:cholesterol acyltransferase (LCAT) as compared to the WT control. The mutant lipid-free apoA-I had normal capacity to promote ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux. The findings indicate that subtle structural alterations in apoA-I may alter the stability and functions of apoA-I and high-density lipoprotein (HDL) and may cause hypertriglyceridemia.
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PMID:Substitutions of glutamate 110 and 111 in the middle helix 4 of human apolipoprotein A-I (apoA-I) by alanine affect the structure and in vitro functions of apoA-I and induce severe hypertriglyceridemia in apoA-I-deficient mice. 1530 43

Apolipoprotein E2 (apoE2) and apoE3-Leiden cause chylomicron remnant accumulation (type III hyperlipidemia). However, the degree of dyslipidemia and its penetrance are different in humans and mice. Remnant uptake by isolated liver from apoE-/- mice transgenic for human apoE2, apoE3-Leiden, or apoE3 was measured. In the presence of both LDL receptor (LDLR) and LDL receptor-related protein (LRP), remnant uptake was apoE3>E3-Leiden>E2 mice. Absence of LDLR reduced uptake in apoE3 and apoE3-Leiden-secreting livers but not in apoE2-secreting livers. LRP inhibition with receptor-associated protein reduced uptake in apoE3- and apoE2-secreting livers, but not in apoE3-Leiden-secreting livers, regardless of the presence of LDLR. Fluorescently labeled remnants clustered with LRP in apoE3-secreting livers only in the absence of LDLR, but clustered in livers that expressed apoE2 even in the presence of LDLR, and did not cluster with LRP in livers of apoE3-Leiden even in the absence of LDLR. Remnants were reconstituted with the three human apoE isoforms. Removal by liver of mApoe-/-/mldlr-/- mice expressing the human LDLR was slightly greater than removal in the previous experiments with apoE3>E2> E3-Leiden. Thus, in vivo, human apoE2 is cleared primarily by LRP, apoE3-Leiden is cleared only by the LDLR, and apoE3 is cleared by both.
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PMID:Chylomicron remnant uptake in the livers of mice expressing human apolipoproteins E3, E2 (Arg158-->Cys), and E3-Leiden. 1546 67

The exchangeable apolipoproteins present in small, dense LDL (sdLDL) and large, buoyant LDL subclasses were evaluated with a quantitative proteomic approach in patients with the metabolic syndrome and with type 2 diabetes, both with subclinical atherosclerosis and the B LDL phenotype. The analyses included surface-enhanced laser adsorption/ionization, time-of-flight mass spectrometry, and subsequent identification by mass spectrometry or immunoblotting and were carried out in LDL subclasses isolated by ultracentrifugation in deuterium oxide gradients with near physiological salt concentrations. The sdLDLs of both types of patients were enriched in apolipoprotein C-III (apoC-III) and were depleted of apoC-I, apoA-I, and apoE compared with matched healthy controls with the A phenotype. The LDL complexes formed in serum from patients with diabetes with the arterial proteoglycan (PG) versican were also enriched in apoC-III. In addition, there was a significant correlation between the apoC-III content in sdLDL in patients and the apparent affinity of their LDLs for arterial versican. The unique distribution of exchangeable apolipoproteins in the sdLDLs of the patients studied, especially high apoC-III, coupled with the augmented affinity with arterial PGs, may contribute to the strong association of the dyslipidemia of insulin resistance with increased risk for cardiovascular disease.
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PMID:A proteomic study of the apolipoproteins in LDL subclasses in patients with the metabolic syndrome and type 2 diabetes. 1599 72

There is increasing evidence of cross-talk between dyslipidemia and renin-angiotensin system (RAS) in atherogenesis. Both dyslipidemia and RAS activation enhance the expression of a newly described receptor for oxidized-low density lipoprotein (ox-LDL), lectin-like ox-LDL receptor-1 (LOX-1). We postulated that the blockade of dyslipidemia with rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor and RAS with candesartan, an angiotensin II type 1 receptor blocker, would have a synergistic inhibitory effect on LOX-1 expression and atherogenesis. Apo-E knockout mice were fed a high-cholesterol diet (1% cholesterol, HC-diet) alone, or HC-diet with rosuvastatin (1mg/(kgd)), candesartan (1mg/(kgd)) or with both. Twelve weeks later the extent of atherosclerosis was determined by Sudan IV staining. Apo-E knockout mice on HC-diet had extensive atherosclerosis. Both rosuvastatin and candesartan decreased the extent of atherosclerosis (by 23 and 26%, respectively), despite the HC-diet; however, the combination of rosuvastatin and candesartan reduced atherosclerosis further (by 67%). Rosuvastatin decreased plasma levels of total cholesterol by over 50%, whereas candesartan had no effect. LOX-1 protein expression was found to be markedly up-regulated in HC-diet-fed apo-E knockout mice. While rosuvastatin and candesartan each had a small inhibitory effect on the expression of LOX-1 in the atherosclerotic tissues, the combination totally blocked the up-regulation of LOX-1. P38 mitogen-activated protein kinase (MAPK) expression and phosphorylation were increased in apo-E knockout mice, attenuated by rosuvastatin or candesartan alone, and completely blocked by the combination of the two agents. P44/42 MAPK expression and phosphorylation were not affected by the HC-diet, rosuvastatin, candesartan, or their combination. This study demonstrates the potent effect of rosuvastatin and candesartan on atherogenesis, as well as on the expression of LOX-1 and on the activation of p38 MAPK, but not p44/42 MAPK.
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PMID:Cross-talk between dyslipidemia and renin-angiotensin system and the role of LOX-1 and MAPK in atherogenesis studies with the combined use of rosuvastatin and candesartan. 1600 8

A goal of dietary management of cardiovascular disease risk in patients with obesity and metabolic syndrome is improvement in the atherogenic dyslipidemia comprising elevated triglyceride, reduced high-density lipoprotein (HDL) cholesterol, and increased numbers of small, dense low-density lipoprotein (LDL) particles. Individuals with a genetically influenced trait characterized by a high proportion of small, dense LDL (phenotype B) respond to a low-fat, high-carbohydrate diet with greater reduction of LDL cholesterol, apoprotein B, and mid-sized LDL2 particles than unaffected subjects (phenotype A). In contrast, in phenotype A subjects there is a reciprocal shift from large LDL1 to small LDL3 such that a high proportion convert to phenotype B. There is evidence for heritable effects on these diet-induced subclass changes and for the involvement of specific genes. For example, a haplotype of the APOA5 gene associated with increased plasma triglyceride and small, dense LDL predicts greater diet-induced reduction of LDL2, a haplotype-specific effect that is strongly correlated with both increased VLDL precursors and LDL4 products. Understanding of such diet-genotype interactions may help to elucidate mechanisms that are responsible for phenotype B and for its differential dietary responsiveness. This information may also ultimately help in identifying those individuals who are most likely to achieve cardiovascular risk benefit from specific dietary interventions.
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PMID:Dietary and genetic probes of atherogenic dyslipidemia. 1616 63

Cardiovascular disease is one of the most important causes of morbidity and mortality in children with end-stage renal failure. Chronic inflammation and malnutrition have been suggested to be risk factors for cardiovascular disease. However, to date, biomarkers of inflammation have not been well studied in children. The aim of this study was to investigate the relation between chronic inflammation and cardiovascular risk factors in children on hemodialysis therapy. Twenty-seven patients on hemodialysis (14 girls, 13 boys) of mean age 15.3 +/- 2.4 years and 20 healthy children (13 girls, 7 boys) of mean age 14.3 +/- 2.7 years were included the study. C-reactive protein (CRP), albumin, prealbumin, transferrin, ferritin, and fibrinogen were measured as the markers of inflammation. The levels of CRP, ferritin, and erythrocyte sedimentation rate among hemodialysis patients were significantly higher than those of control subjects (P < .001 for all). Albumin and transferrin levels were found to be lower than those of control group (P = .02 and P < .001, respectively). CRP levels were negatively correlated with albumin, prealbumin, apoprotein A1, HDL, and hemoglobin levels, and positively correlated with erythropoietin/Htc ratios. This study suggests that hemodialyzed children are exposed to chronic inflammation. In addition, CRP may be an indicator of chronic inflammation related to cardiovascular risk factors, such as malnutrition, dyslipidemia, and anemia. In conclusion, we suggest that the risk of cardiovascular disease could be reduced by defining markers of chronic inflammation and malnutrition in hemodialyzed children and by taking necessary measures at an early stage.
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PMID:Relationship between chronic inflammation and cardiovascular risk factors in children on maintenance hemodialysis. 1621 60

Studies were carried out in 183 non-dialyzed, 123 hemodialysis, 81 continuous ambulatory peritoneal dialysis and 35 post-transplant patients and in 103 healthy subjects as a reference group. Lipids and apolipoprotein (apo)AI and apoB were determined using Roche kits. An anti-apoB antibody was used to separate apoB-containing apoCIII and apoE-triglyceride-rich lipoprotein (TRL) in the non-high-density lipoprotein (non-HDL) fraction from apoCIIInonB and apoEnonB in the HDL fraction in four groups of patients with chronic renal failure (CRF) and healthy subjects. Multivariate linear regression analysis was used to investigate the relationship between triglyceride (TG) or HDL-cholesterol (HDL-C) concentrations and lipoproteins. Dyslipidemia varied according to the degree of renal insufficiency, the type of dialysis and therapy regime in CRF patients. Lipoprotein disturbances were manifested by increased TG, non-HDL-C and TRL concentrations, and decreased HDL-C and apoAI concentrations, whereas post-renal transplant patients showed normalization of lipid and lipoprotein profiles, except for TG levels and total apoCIII and apoCIIInonB. The present study indicates that CRF patients have disturbed lipoprotein composition, and that hypertriglyceridemia and low HDL-C concentrations in these patients are multifactorial, being secondary to disturbed lipoproteins. The method using anti-apoB antibodies to separate apoB-containing lipoproteins in the non-HDL fraction from non-apoB-containing lipoproteins in HDL can be used in the diagnosis and treatment of patients with progression of renal failure or atherosclerosis. The variability of TG and HDL-C concentrations depends on the variability of TRL and cholesterol-rich lipoprotein concentrations, but the decreases in TG and increases in HDL-C concentrations are caused by apoAI concentration variability. These relationships, however, need to be confirmed in further studies.
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PMID:Disturbed lipoprotein composition in non-dialyzed, hemodialysis, continuous ambulatory peritoneal dialysis and post-transplant patients with chronic renal failure. 1637 88

Dyslipidemia and inflammation may promote renal disease via mechanisms of vascular endothelial cell dysfunction in type II diabetes mellitus (DM). Sparse data, however, are available on the relation of lipids and inflammatory biomarkers and glomerular filtration rate (GFR) in type II DM. We performed a cross-sectional study of 732 men with type II DM enrolled in the Health Professionals' Follow-Up Study. Plasma creatinine was used to estimate GFR by the simplified Modification of Diet in Renal Disease (MDRD) equation. In men with a GFR <60 ml/min/1.73 m(2), triglycerides, non-high-density lipoprotein (HDL), apoprotein B, fibrinogen, soluble tumor necrosis factor receptor (sTNFR-2) and vascular cell adhesion molecule-1 (VCAM) were significantly higher when compared to the referent group (GFR> or =90 ml/min/1.73 m(2)). In multivariable logistic regression, those in the highest quartiles of the following biomarkers had increased odds of having a GFR <60 ml/min/1.73 m(2) when compared to those in the lowest quartiles: triglycerides (odds ratio (OR) 3.11; 95% CI, 1.52-6.36), fibrinogen (OR 5.40; 95% CI 2.14-13.65), sTNFR-2 (OR 8.34; 95% CI 3.50-19.88) and VCAM (OR 4.50; 95% CI 1.98-10.23). An inverse association was observed for HDL (OR 0.48; 95% CI 0.24-0.98). We found no association between C-reactive protein and GFR. The results were similar when creatinine clearance by Cockcroft-Gault was used to estimate kidney function. We conclude that several potentially modifiable lipid and inflammatory biomarkers are elevated in the setting of moderately decreased GFR in men with type II DM and may be the link between renal insufficiency and increased risk for cardiovascular events in this population.
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PMID:The association of serum lipids and inflammatory biomarkers with renal function in men with type II diabetes mellitus. 1640 7

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