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)

Patients with end-stage renal disease (ESRD) suffer from a secondary form of complex dyslipidemia consisting of both quantitative and qualitative abnormalities in serum lipoproteins resulting from alterations in lipoprotein metabolism and composition. The prominant features of uremic dyslipidemia are an increase in serum triglyceride levels (due to elevated very low density lipoprotein [VLDL]-remnants and intermediate-density lipoprotein [IDL]) and low high-density lipoprotein (HDL) cholesterol. Low-density lipoprotein (LDL) cholesterol often is normal, but the cholesterol may originate from the atherogenic small and dense LDL subclass (sdLDL). The apolipoprotein B (apoB)-containing part of the lipoprotein may undergo modifications (enzymatic- and advanced glycation end-product [AGE]-peptide modification, oxidation, or glycosilation). Modifications contribute to impaired LDL receptor-mediated clearance from plasma and promote prolonged circulation. While LDL particles undergo a vicious cycle of accumulation and modification, reverse cholesterol transport is also impaired due to low lecithin:cholesterol acyltransferase (LCAT) and paraoxonase activity. Therefore, discoid HDL particles are structurally altered and hepatic cholesterol clearance is limited. The composition of HDL may also be altered during states of inflammation. The contribution of this complex and atherogenic form of dyslipidemia to cardiovascular disease in patients with renal disease is unclear at present. Most studies are negative in demonstrating the predictive power of serum lipids for the development of cardiovascular disease. This is most likely due to interference with deteriorating aspects of the activated acute-phase response. Nevertheless, patients with renal disease belong to a very high cardiovascular risk group and dyslipidemia should most likely be subjected to sufficient lipid-lowering therapy in most patients. Because it is also still unclear whether we have available therapies with sufficient impact on LDL size, remnant lipoprotein-lowering, and restoration of HDL function, we urgently need the results from large scale intervention trials such as the 4D-trial and the CHORUS study.
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PMID:Abnormalities in uremic lipoprotein metabolism and its impact on cardiovascular disease. 1157 15

A three-month administration of phensuccinal improved glucose homeostasis, decreased the levels of total cholesterol, triglycerides, fatty acids, and low-density lipoproteins in the blood serum, and reduced the lipid peroxidation rate as compared to the untreated diabetic control. In addition, phensuccinal increased the content of the antiatherogenic high-density lipoprotein fraction and the related paraoxonase enzyme activity. The preventive effect of phensuccinal with respect to diabetic dyslipidemia development, together with the antioxidant action, show this compound to be a promising therapeutic means of preventing and/or reducing macrovascular complications in diabetic patients.
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PMID:[Effect of phensuccinal on lipid metabolism, lipid peroxidation, and antioxidant system activity in rabbits with dithiazone-induced diabetes]. 1455 51

Preeclampsia is one of the most frequent complications of pregnancy, however, little is known about its etiology. The objective of this study was to investigate the association of oxidized low-density lipoprotein (oxLDL) and paraoxonase (PON1) activity in women with either preeclampsia or normotensive (NT) pregnancy. The study groups included 41 pregnant women with preeclampsia and 33 normotensive pregnant women. In all patients maternal serum total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs) were measured using enzymatic methods. Serum PON1 activities and malondialdehyde (MDA) concentrations were measured by spectrophotometric methods, and oxLDL was measured by enzyme-linked immunoassay (ELISA). Serum concentrations of lipid parameters (TC, LDL, VLDL, and TGs) were significantly higher in preeclampsia compared with NT controls (p < 0.001, p < 0.05, p < 0.05, and p < 0.001, respectively). Serum concentrations of MDA and oxLDL were significantly higher, while PON1 activity was significantly lower in preeclampsia compared with NT controls (p < 0.001, p < 0.001, and p < 0.001, respectively). A positive correlation was detected between oxLDL and MDA (r = 0.876), and a negative correlation was detected between both MDA and oxLDL and PON1 (r = -0.837 and r = -0.759, respectively). Our data demonstrate that preeclampsia is associated with increased oxLDL and decreased PON1 activity. Elevated oxidative stress, oxLDL, dyslipidemia and decreased PON1 activities may cause vascular endothelial damage and contribute to the pathophysiology of preeclampsia.
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PMID:Circulating oxidized low-density lipoprotein and paraoxonase activity in preeclampsia. 1608 95

Cardiovascular disease is a leading cause of mortality in rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest atherosclerosis. Both traditional, Framingham risk factors and inflammation-associated factors are involved in RA-associated atherosclerosis. Among imaging techniques, the early determination of common carotid intima-media thickness (ccIMT), flow-mediated vasodilation (FMD), and nitroglycerine-mediated vasodilation (NMD) may be useful to determine atherosclerosis and endothelial dysfunction. We and others found increased ccIMT and impaired FMD in RA patients. Among immunological and metabolic laboratory markers, anticyclic citrullinated peptide (anti-CCP) antibodies, IgM rheumatoid factor, circulating immune complexes, pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), Th0/Th1 T cells, homocysteine, dyslipidemia, decreased folate and vitamin B12 production, and impaired paraoxonase activity may all be involved in the development of vascular disease in RA. The early diagnosis of endothelial dysfunction and atherosclerosis, active immunosuppressive treatment, the use of drugs that control atherosclerosis, changes in sedentary lifestyle, and the close follow-up of RA patients may help to minimize cardiovascular risk in these individuals.
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PMID:Accelerated atherosclerosis in rheumatoid arthritis. 1789 98

The metabolic syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is a primary risk factor for diabetes and cardiovascular disease. We showed for the first time that the metabolic syndrome is associated with a higher fraction of oxidized LDL and thus with higher levels of circulating oxidized LDL. Hyperinsulinemia and impaired glycaemic control, independent of lipid levels, were associated with increased in vivo LDL oxidation, as reflected by the higher prevalence of high oxidized LDL. High levels of oxidized LDL were associated with increased risk of future myocardial infarction, even after adjustment for LDL-cholesterol and other established cardiovascular risk factors. This association is in agreement with the finding that accumulation of oxidized LDL, which activates/induces subsets of smooth muscle cells and macrophages to gelatinase production, was associated with upstream localization of a vulnerable plaque phenotype. Dyslipidemia and insulin resistance in obese LDL receptor-deficient mice were associated with increased oxidative stress and impaired HDL-associated antioxidant defence associated with accelerated atherosclerosis due to increased macrophage infiltration and accumulation of oxidized LDL in the aorta. The accumulation of oxidized LDL was partly due to an impaired HDL-associated antioxidant defence due to a decrease in PON. Our data in this experimental model are thus the more relevant because a decrease in PON activity was found to be associated with a defective metabolism of oxidized phospholipids by HDL from patients with type 2 diabetes. Weight loss in leptin-deficient, obese, and insulin-resistant mice was associated with expressional changes of key genes regulating adipocyte differentiation, glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. We established an important relationship between PPAR-gamma and SOD1 for the prevention of the oxidation of LDL in the arterial wall. For example we showed that rosuvastatin decreased the oxidized LDL accumulation by increasing the expression of PPAR-gamma and SOD1. In addition, we established a relation between increased PPAR-alpha expression in the adipose tissue and a change in the gene expression pattern, which explains the decrease of free fatty acids, triglycerides and the increase in insulin sensitivity. We demonstrated that plaque oxidized LDL correlated with coronary plaque complexity in a swine atherosclerosis model. Oxidized LDL correlated positively with the expression of IRF1 and TLR2 suggesting a relation between oxidative stress and inflammation in coronary atherosclerotic plaques. Oxidized LDL induced further the expression of TLR2 and IRF1 in macrophages in vitro suggesting a causative link. As in the mouse model described above, plaque oxidized LDL correlated negatively with SOD1 expression and ox-LDL inhibited the expression of SOD1 in macrophages in vitro. We showed that TLR2, CXCR4 and MYC are overexpressed in monocytes of obese women at high cardiovascular risk and that weight loss was associated with a concomitant decrease of their expression. This suggests that the transcription factor cMYC has an atherogenic effect by inducing pro-inflammatory genes. The increased expression of TLR2 and CXCR4 were observed in the absence of an increase in ox-LDL but in the presence of an increase in SOD1. Interestingly, the expression of SOD1 correlated also with that of MYC, suggesting that it has an atherogenic effect by inducing the expression of an anti-oxidant enzyme. How ox-LDL prevents this increase remains to be determined. How we plan to do this is explained in the next part. In aggregate, our studies contributed to a better understanding of the relationships between metabolic syndrome, insulin signalling, oxidative stress and inflammation and atherosclerosis. We identified paraoxonase, interferon regulatory factor-1, toll-like receptors, CXCR4 and SOD1 as possible targets for intervention.
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PMID:Relations between metabolic syndrome, oxidative stress and inflammation and cardiovascular disease. 1866 60

The paraoxonase (PON) gene family has 3 members, PON1, PON2 and PON3, which are known to be involved in oxidative stress-associated processes such as dyslipidemia, diabetes and coronary heart disease. Although PON3 is the least studied paraoxonase, recent findings have shown that it can significantly reduce atherosclerotic lesion formation and obesity in PON3 transgenic mice. Here, we describe the isolation and molecular characterization of the cDNA encoding the porcine PON3 gene. We also report the cloning of three porcine PON3 transcript variants resulting from alternate splicing of exons. Our results show that PON3 mRNA and protein are ubiquitously expressed in pig tissues. Moreover, the relative abundance of PON3 mRNA, measured in perirenal and subcutaneous fat tissues, is higher in obese Upton Meishan gilts compared with the leaner Large White and Ham Line gilts. PON3 mRNA levels measured in fat tissues positively correlate with subcutaneous, visceral and total body fat weights. Four single nucleotide polymorphisms (SNP) were identified in the PON3 coding sequence, and among these, an association was found between the c.449G>A polymorphism and the longissimus dorsi depth estimated breeding value (EBV) trait. Knowledge of the structure, distribution and expression profile of the porcine PON3 gene provides insights into its physiological function. Our results provide further support for involvement of PON3 in obesity-related disorders.
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PMID:Molecular characterization and expression analysis of the porcine paraoxonase 3 (PON3) gene. 1942 87

Dyslipidaemia including decreased high density lipoprotein cholesterol concentration is one of several factors that have been implicated in increased cardiovascular risk. Since their introduction in the 1980s, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have emerged as the one of the best-selling class of medications to date, with numerous trials demonstrating powerful efficacy in preventing cardiovascular diseases. Although statins have been shown to modestly raise or not alter HDL-cholesterol, their effect on HDL subfractions and on HDL-associated enzymes including human paraoxonase-1 (PON1) has not yet been fully explored. This review summarizes the currently available data on the effect of statins on HDL subfractions and on PON1 activity with a particular emphasis on the clinical relevance of these effects. Moreover, methodological problems of HDL subfraction and PON1 activity determinations are also discussed.
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PMID:Benefits and difficulties in measuring HDL subfractions and human paraoxonase-1 activity during statin treatment. 1985 94

The aim of this study was to determine the cardiovascular disease risk factors (risk of overweight/overweight, dyslipidemia, paraoxonase-1 activity, positive family history, physical inactivity, smoking) that accompany hypertension and investigate the relationship between hypertension and some of these risk factors. This study included 118 hypertensives and 118 age- and sex-matched non-hypertensive controls aged 12-14 years. Among controls, 64.4% had no risk factor. Among cases, 34.8% had no risk factor other than hypertension, and 65.2% had two or more risk factors. The adjusted odds ratio (OR) (95% confidence interval [CI]) of hypertension was 5.65 (2.88-11.09) for risk of overweight/overweight. Body mass index, paraoxonase and arylesterase activities were significantly higher in hypertensives than those of the control group. We conclude that it would be useful to routinely evaluate blood pressure and body weight at schools and, additionally, considering that hypertension alone is encountered rarely, it would be appropriate to examine the hypertensive students for other risk factors.
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PMID:Hypertension in children (12-14 years)--a case-control study in Bursa, Turkey. 2011 98

Dyslipidemia in patients with glycogen storage disease types Ia (GSD Ia) and III (GSD III) does not lead to premature atherosclerosis. The aim of this study was to investigate the association among serum copper (Cu), zinc (Zn), iron (Fe), and selenium (Se) concentrations, and their carrier proteins: ceruloplasmin, albumin, and related antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), paraoxonase (PON), and arylesterase (ARYL)] in 20 GSD Ia and 14 III patients compared to age and sex matched 20 healthy subjects. Erythrocyte oxidative stress was measured by erythrocyte thiobarbituric acid reactive substances (eTBARSs). Hypertriglyceridemia [333 (36-890)mg/dL] in GSD Ia and hypercholesterolemia with elevated LDL-cholesterol [188 (91-313)mg/dL] and decreased HDL-cholesterol [32(23-58)mg/dL] levels in GSD III were found. Serum Cu, Fe, and Zn showed no significant differences between groups. However, Se 60 (54-94), 81 (57-127) microg/L, ceruloplasmin 21 (10-90), 27 (23-65) microg/L, and albumin 2.4 (1.7-5.1), 2.8 (1.8-4.06)g/dL levels were decreased in GSD Ia and III groups, respectively, in comparison with the controls [Se 110 (60-136) microg/L, ceruloplasmin 72 (32-94) microg/L, and albumin 4.4 (4-4.8)g/dL)]. In spite of high oxidative stress in erythrocyte detected by elevated eTBARS/Hb levels in GSD group [674.8 (454.6-948.2) for GSD Ia, 636.3 (460.9-842.1) for GSD III, and 525.6 (449.2-612.6)], the activities of CAT, SOD, ARYL, and PON in GSD patients were not different from the controls. GPx activity was decreased in GSD Ia [3.7 (1.8-7.1)U/mL] and GSD III [4.2 (2.2-8.6)U/mL] compared with healthy controls [7.1 (2.9-16.2)U/mL]. In conclusion, this study supplied the data for trace elements, their carrier, and antioxidative enzymes in the patients with GSD Ia and III. The trace elements and anti-oxidative enzyme levels in GSD patients failed to explain the atherosclerotic escape phenomenon reported in these patients.
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PMID:An association among iron, copper, zinc, and selenium, and antioxidative status in dyslipidemic pediatric patients with glycogen storage disease types IA and III. 2012 79

Paraoxonase-1 (PON1, EC 3.1.8.1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme, and its activity correlates negatively with the level of plasma low-density lipoprotein cholesterol (LDL-C) and triglyceridemia (TG). In this study, we examined the therapeutic effect of plasmid DNA containing the human PON1 gene (pcDNA/PON1) in hyperlipidemic model rats. The rats were fed a high-fat and high-cholesterol diet for 25 days to produce a hyperlipidemic animal model. Single intravenous injection of pcDNA/PON1 into model rats prevented dyslipidemia and hepatic lipid accumulation. The mechanisms of pcDNA/PON1 in treating hyperlipidemia were associated with increases of serum antioxidant PON1 and SOD activities, and with reduction of the levels of total cholesterol (TC), LDL-C and TG. The results suggest the potential therapeutic effect of pcDNA/PON1 on hyperlipidemia.
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PMID:Single intravenous injection of plasmid DNA encoding human paraoxonase-1 inhibits hyperlipidemia in rats. 2058 Jun 87

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