LDL Subfractions In Patients Research Articles

Relationship between serum Betatrophin, GPIHBP1, and LDL subfractions in patients with gestational diabetes mellitus

ObjectivesGestational diabetes mellitus (GDM) leads to changes in the lipid metabolism. In this study, we aimed to compare serum levels of LDL subfractions, betatrophin, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) between patients with GDM and healthy pregnant women. Design and MethodsWe designed a prospective case-control study with 41 pregnant women. Subjects were divided into two groups: GDM and control. Betatrophin and GPIHBP1 levels were measured by ELISA method. Lipoprint LDL subfraction kit was used to perform LDL subfraction analysis electrophoretically. ResultsSerum levels of LDL6 subfraction, betatrophin, and GPIHBP1 were found to be higher in GDM group compared to the controls (p < 0.001). The mean LDL size were also found larger in GDM group. A positive correlation was found between betatrophin and GPIHBP1 levels (rho = 0.96, p < 0.001). ConclusionsOur findings suggest that betatrophin, and GPIHBP1 levels were found to be increased in GDM. This maybe the result of adaptive mechanisms in response to insulin resistance, but also this relationship should be evaluated for their effects on impaired lipid metabolism and lipoprotein lipase metabolism. There is a need for further prospective studies with larger samples to fully elucidate the mechanisms of this relationship both in pregnant patients and the other patient groups.

Effect of Non-Statin Lipid Lowering and Anti-Obesity Drugs on LDL Subfractions in Patients with Mixed Dyslipidaemia

Small, dense low density lipoprotein (sdLDL) particles are considered an emerging cardiovascular risk factor. Obese patients with mixed dyslipidaemia frequently have elevated sdLDL cholesterol (sdLDL-C) levels. Therefore, agents that favourably modulate the LDL phenotype may be of clinical value in these patients. We review the efficacy of anti-obesity and lipid lowering drugs other than statins on LDL subfractions in patients with mixed dyslipidaemia primarily focusing on those who are overweight/obese. The literature search was based on PubMed listings up to 26 November 2009. In most studies ezetimibe decreases the large and medium LDL subclasses and, to a lesser extent, the sdLDL particles, while it does not substantially influence LDL size. Fibrates and niacin reduce sdLDL particles and shift LDL size towards large, buoyant LDL particles. More studies are needed to elucidate the effects of fish oils and resins on LDL phenotype. Orlistat and rimonabant have been associated with reductions in sdLDL-C levels along with an increase in LDL particle size. We did not find any literature describing the effect of sibutramine on sdLDL profile. Treatment with fibrates and niacin seems to be beneficial in patients with mixed dyslipidaemia. The addition of orlistat may further improve LDL phenotype in overweight/obese patients.

We-P11:104 LDL subfractions in patients with metabolic syndrome

We-P11:104 LDL subfractions in patients with metabolic syndrome

Linoleic Acid Increases Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in Human Aortic Endothelial Cells

Results from in vitro studies suggest that selected fatty acids, and especially linoleic acid (LA), can elicit endothelial dysfunction (ED). Because LA is increased in all LDL subfractions in patients with type 2 diabetes, this alteration may contribute to ED associated with diabetes. Lectin-like oxidized LDL receptor-1 (LOX-1) is the major endothelial receptor for oxidized LDL (oxLDL), and uptake of oxLDL through LOX-1 induces ED. To evaluate whether LA may contribute to the upregulation of endothelial LOX-1 in diabetes, we studied the effect of LA on LOX-1 expression in cultured human aortic endothelial cells (HAECs). Treatment of HAECs with LA increased, in a time- and dose-dependent manner, endothelial LOX-1 protein expression. Pretreatment of HAECs with antioxidants and inhibitors of NADPH oxidase, protein kinase C (PKC), and nuclear factor-kappaB (NF-kappaB) inhibited the stimulatory effect of LA on LOX-1 protein expression. Furthermore, in LA-treated HAECs, increased expression of classic PKC isoforms was observed. LA also led to a significant increase in LOX-1 gene expression and enhanced the binding of nuclear proteins extracted from HAECs to the NF-kappaB regulatory element of the LOX-1 gene promoter. Finally, LA enhanced, through LOX-1, oxLDL uptake by endothelial cells. Overall, these results demonstrate that LA enhances endothelial LOX-1 expression through oxidative stress-sensitive and PKC-dependent pathways. This effect seems to be exerted at the transcriptional level and to involve the activation of NF-kappaB. Upregulation of LOX-1 by LA may contribute to ED associated with type 2 diabetes.

In vivo metabolism of LDL subfractions in patients with heterozygous FH on statin therapy: rebound analysis of LDL subfractions after LDL apheresis

LDL can be subfractionated into buoyant (1.020-1.029 g/ml(-1)), intermediate (1.030-1.040 g/ml(-1)), and dense (1.041-1.066 g/ml(-1)) LDLs. We studied the rebound of these LDL-subfractions after LDL apheresis in seven patients with heterozygous familial hypercholesterolemia (FH) regularly treated by apheresis (58 +/- 9 years, LDL-cholesterol = 342 +/- 87 mg/dl(-1), triglycerides = 109 +/- 39 mg/dl(-1)) and high-dose statins. Apolipoprotein B (apoB) concentrations were measured in LDL subfractions immediately after and on days 1, 2, 3, 5, and 7 after apheresis. Compartmental models were developed to test three hypotheses: 1) that dense LDLs are derived from the delipidation of buoyant and intermediate LDLs (model A); 2) that dense LDLs are generated directly from LDL-precursors (model B); or 3) that a model combining both pathways (model C) is necessary to describe the metabolism of dense LDLs. In all models, it was assumed that apoB production and fractional catabolic rate (FCR) did not change with apheresis. Apheresis decreased buoyant, intermediate, and dense LDL-apoB by 60 +/- 12%, 67 +/- 5%, and 69 +/- 11%, respectively. Models B and C, but not model A, described the rebound data. The model with the greatest biological plausibility (model C) was used to estimate metabolic parameters. FCR was 1.05 +/- 0.86 d(-1), 0.48 +/- 0.11 d(-1), and 0.69 +/- 0.24 d(-1) for buoyant, intermediate, and dense LDLs, respectively. Dense LDL production was 17.3 +/- 0.2 mg/kg(-1)/d(-1), 58% of which was derived directly from LDL precursors (VLDL, IDL, or direct secretion), while 42% was derived from buoyant and intermediate LDLs. Thus, our data indicate that in statin-treated patients with heterozygous FH dense LDLs originate from two sources. Whether this is also valid in other metabolic situations (with predominant small, dense LDLs) remains to be determined.

M.669 Effect of fenofibrate on LDL subfractions in patients with combined dyslipidemia

M.669 Effect of fenofibrate on LDL subfractions in patients with combined dyslipidemia

M.669 Effect of fenofibrate on LDL subfractions in patients with combined dyslipidemia

The aim of this study was to assess the influence of ischemic preconditioning (IPC) on parenchymal liver blood flow during the early phase of reperfusion after 60 minutes of ischemia, additionally modified by adding N-nitro-L-arginine methyl ester (L-NAME). Our research involved 4 groups of rats (10 animals in each group), which underwent liver ischemia and 24 hours of reperfusion. Group I, ischemia/reperfusion (IR) was performed; group II, IPC, 10 minutes of ischemia and 10 minutes of reperfusion, and IR after that; group III, L-NAME (10 mg/kg intravenous [iv]), 10 minutes before IR; and group IV, L-NAME before IPC + IR. Activity of APAT, ALAT, GGTP, and FA was marked in serum in 90 minutes and 24 hours of reperfusion. In the liver biopsies at 24 hours of reperfusion, we analyzed reaction on adenosine-3-phosphatase stimulated by Mg++ and performed histological examination. The parenchymal perfusion was measured using a laser-doppler blood flowmeter (model PeriFlux System5000, Perimed Inc., United Kingdom). IPC during reperfusion led to minor injuries of the organ, with statistically significant normalization of enzymes compared with group 1, and a better reaction to the adenosine-3-phosphatase IPC produced faster and full return of perfusion to the 68.3 value at 24 hours (59.1 in the 60 minutes). In groups III and IV at 60 minutes, the perfusion was not statistically different from that in group 1. IPC causes full and faster blood return in the early phase of reperfusion and minor injury of liver parenchyma and liver sinus. The protective effect observed, especially in the first 60 minutes of reperfusion, was limited by L-NAME and was influenced by the action of nitric oxide.

2P-0558 Effects of atorvastatin treatment on plasma ultracentrifugally separated LDL subfractions in patients with FH and FCHL

2P-0558 Effects of atorvastatin treatment on plasma ultracentrifugally separated LDL subfractions in patients with FH and FCHL

Short‐term antioxidant supplementation reduces oxidative stress in elderly patients with type 2 diabetes mellitus—a pilot study

AbstractAimsThe aim of this pilot study was to determine what dose of which antioxidants might be studied in clinical trials by assessing the impact of vitamin (C and E) supplementation on markers of oxidative stress and LDL subfractions in patients with type 2 diabetes mellitus.MethodsNine elderly patients with type 2 diabetes took a moderate dose combination of vitamins C (500 mg) and E (400 IU) for 4 weeks. Following a 4 week washout, the patients had a further 4 weeks of supplementation with a higher dose combination of vitamins C (1000 mg) and E (800 IU). Blood was sampled pre‐ and post‐supplementation for vitamin E by high‐performance liquid chromatography (HPLC), total antioxidant capacity by enhanced chemiluminescence, total cholesterol and lipid hydroperoxides by colour spectrophotometry and LDL subfraction profile by disc polyacrylamide gel electrophoresis.ResultsVitamin E was increased, after the moderate dose combination (59.8 ± 6 versus 36.4 ± 4 µmol/L, p &lt; 0.001) and increased further by the higher dose (72.7 ± 11 versus 30.8 ± 5 µmol/L, p &lt; 0.001). Total antioxidant capacity was significantly increased above baseline after both doses (508.2 ± 33 versus 436.4 ± 31, p &lt; 0.01 (moderate); 519.3 ± 48 versus 440.8 ± 34 µmol/L trolox eq., p &lt; 0.01 (high)). Lipid hydroperoxides were reduced more after the moderate dose combination than after the high dose (6.1 ± 1 versus 12.1 ± 2, p &lt; 0.01; 8.0 ± 1 versus 11.6 ± 1 µmol/L, p &lt; 0.05). LDL subfraction score showed a non‐significant reduction after both periods of supplementation.ConclusionsThis study has demonstrated that supplementation with modest doses of the antioxidant vitamins C and E can significantly increase antioxidant defences and reduce oxidative damage in elderly patients with type 2 diabetes. Copyright © 2002 John Wiley &amp; Sons, Ltd.

Influence of simvastatin on LDL-subtypes in patients with heterozygous familial hypercholesterolemia and in patients with diabetes mellitus and mixed hyperlipoproteinemia.

This study evaluates the influence of simvastatin on lipid concentrations and on LDL-subtype distribution in patients with heterozygous familial hypercholesterolemia and in patients with type 2 diabetes and mixed hyperlipoproteinemia. Nine patients with familial hypercholesterolemia (LDL-cholesterol: 7.1 +/- 1.1 mmol/L, triglycerides: 1.3 +/- 0.4 mmol/L) and 8 patients with type 2 diabetes mellitus and mixed hyperlipoproteinemia (HbA1c 6.8 +/- 1.1%, LDL-cholesterol: 4.8 +/- 0.7 mmol/L, triglycerides: 2.5 +/- 1.1 mmol/L) were examined. Cholesterol concentration was determined in 7 LDL-subfractions isolated by density gradient ultracentrifugation before and during simvastatin treatment (10-20 mg/d, 4 weeks). Simvastatin decreased LDL-cholesterol (-34%/-30%, all p < 0.05) and triglycerides (-2%, n.s./-25%, p < 0.05), but had little effect on HDL-cholesterol (+7%/+2%, n.s.) in patients with familial hypercholesterolemia and diabetes mellitus, respectively. In both groups a significant reduction of cholesterol in each LDL-subfraction was observed. Large-buoyant (LDL-1, LDL-2) and intermediate-dense (LDL-3, LDL-4) LDL were reduced more than small-dense (LDL-5-LDL-7) LDL-subtypes (-36%/-38%/-23%, respectively) in patients with familial hypercholesterolemia, while in diabetic patients cholesterol reduction was uniform in all LDL-subtypes (-29%/-27%/-31%, respectively). Simvastatin decreases cholesterol concentration in all LDL-subfractions in patients with familial hypercholesterolemia and in patients with diabetes mellitus with mixed hyperlipoproteinemia. However, the relative reduction of individual LDL-subtypes differed between both groups. This suggests that the effect of simvastatin on LDL-subtype distribution depends on the type of underlying hyperlipoproteinemia.

LDL subfractions in patients with myocardial infarction: effect of smoking and beta-blocker treatment.

The aim of the present case-control study was to estimate, by density gradient ultracentrifugation, LDL heterogeneity in myocardial infarction, and to evaluate the effect of smoking and beta-blocker treatment on LDL subfraction profile. Our results show that patients who survive myocardial infarction have an abundance of small, dense LDL in their plasma, compared with controls. Patients who were on beta-blockers and those who smoked showed a more atherogenic LDL subfraction profile than the rest. In patients on beta-blocker treatment, the proportion of LDL3 was positively correlated with triglyceride concentration and body mass index. Dense LDL predominates in patients irrespective of smoking or beta-blocker treatment. The relative risk, calculated by logistic regression as the odds ratio of high LDL3, was 7.5 (95% confidence interval 2.5-22.1) and was not significantly influenced when smoking, beta-blocker treatment, triglycerides or the other parameters of the study were included in the statistical model.