CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2008
Ran Fu
SUMMARY 1We sought to determine the effects of Q192R polymorphism of paraoxonase 1 (PON1) gene on plasma high-density lipoprotein,cholesterol (HDL-C) levels and the response to statin therapy in Chinese patients with coronary heart disease (CHD). 2Two hundred and thirty-six patients with CHD were treated with simvastatin 20 mg/day. Fasting serum lipids were determined before and after 12 weeks of treatment. 3No significant differences were detected among the PON1 Q192R polymorphism with respect to plasma lipids. In addition, the effects of simvastatin to increase HDL-C levels were significantly greater in patients with the RR genotype compared with patients with the QR or RR genotypes (P < 0.05). 4We conclude that the Q192R polymorphism of PON1 significantly modulates the HDL-C response to simvastatin in Chinese patients with CHD. [source]

OXIDIZED LOW-DENSITY LIPOPROTEIN INDUCES ENDOTHELIAL PROGENITOR CELL SENESCENCE, LEADING TO CELLULAR DYSFUNCTION

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2004
Toshio Imanishi
SUMMARY 1.,Recent studies have revealed an association between coronary risk factors and both the number and function of bone marrow-derived endothelial progenitor cells (EPC). We investigated the effect of oxidized low-density lipoprotein (ox-LDL) on the senescence of EPC, leading to cellular dysfunction. 2.,Endothelial progenitor cells were isolated from human peripheral blood and characterized. The exposure of cultured EPC to ox-LDL (10 µg/mL) significantly accelerated the rate of senescence compared with control during 20 days in culture as determined by acidic ,-galactosidase staining. Oxidized LDL-induced EPC senescence was significantly inhibited by pretreatment with either lectin-like ox-LDL receptor-1 (LOX-1) antibody (Ab) or atorvastatin (P < 0.01). 3.,Because cellular senescence is critically influenced by telomerase, which elongates telomeres, we measured telomerase activity using a polymerase chain reaction,ELISA-based assay. Oxidized LDL significantly diminished telomerase activity to approximately 50%, an effect that was significantly abolished by pretreatment with either LOX-1 Ab or atorvastatin (P < 0.01). 4.,We examined whether ox-LDL-induced EPC senescence translates into EPC dysfunction. An MTS assay disclosed an inhibitory effect of ox-LDL on EPC proliferation. In a Matrigel assay, EPC treated with ox-LDL were less likely to participate in network fomation compared with controls. 5.,In conclusions, ox-LDL accelerates the onset of EPC senescence, which may be related to telomerase inactivation. Oxidized LDL-induced EPC senescence leads to the impairment of proliferative capacity and network formation. [source]

Lipoprotein (a) in Chronic Renal Failure: Effect of Maintenance Hemodialysis

HEMODIALYSIS INTERNATIONAL, Issue 4 2003
Om Prakash Kalra
Background:,Coronary artery disease accounts for significant morbidity and mortality in patients with chronic kidney disease (CKD). Besides the higher prevalence of traditional risk factors, several uremia-related factors may play a role in accelerated atherosclerosis, such as elevated levels of lipoprotein (a) (Lp(a)). The effect of maintenance hemodialysis (MHD) on Lp(a) levels is not well understood. The present work was carried out to study the Lp(a) levels in Stage 4 and Stage 5 CKD patients as well as the effect of MHD on Lp(a) levels in patients with Stage 5 CKD. Methods:,The study subjects included 15 patients with Stage 4 CKD, 15 patients with Stage 5 CKD, and 15 age- and sex-matched healthy controls. Plasma Lp(a) was measured by ELISA in all the subjects at the time of entry into the study and after 4 weeks of MHD in patients with Stage 5 CKD. Patients on MHD were dialyzed two to three times weekly for 4 hr during each session. Results:,Mean Lp(a) levels were significantly higher in patients with CKD than in control patients. In patients with Stage 4 CKD, the Lp(a) level was 34.0 ± 19.5 mg/dL, whereas in Stage 5 CKD the level was 49.0 ± 30.9 and in healthy controls it was 22.2 ± 16.4. In patients with Stage 5 CKD, 4 weeks of MHD led to a significant fall in Lp(a) levels by 23.6% (P < 0.001). Conclusions:,The results of this study show that increases in Lp(a) levels start early during the course of CKD and become more pronounced with increased severity of disease. Initiation of MHD lowers Lp(a) levels and may have a long-term beneficial effect on cardiovascular morbidity and mortality. [source]

Lipoprotein(a) in patients initiating antiretroviral therapy

HIV MEDICINE, Issue 6 2008
S Mauss
Objectives The interaction between lipoprotein(a), an emerging cardiovascular risk factor, and antiretrovirals (ARVs) has been less well studied than the interaction between either cholesterol or triglycerides and these drugs. In this study we assessed the effect of initiating antiretroviral therapy (ART) on lipoprotein(a) levels. Methods Fasting samples from 95 patients initiating ART with nucleoside/nucleotide reverse transcriptase inhibitors plus nonnucleoside reverse transcriptase inhibitors or protease inhibitors were obtained. Lipids and lipoproteins were determined until week 48. Results As in the general population, the study population showed a highly skewed lipoprotein(a) distribution (median 9.9 mg/dL, range 0.1,110 mg/dL). The study population was divided into individuals with lipoprotein(a) ,30 mg/dL at baseline (n=28) and those with <30 mg/dL (n=67). Almost exclusively, patients with high lipoprotein(a) at baseline (median 51.6 mg/dL) showed a profound increase of median 26.7 mg/dL (week 24). This effect was not associated with specific ARVs and was independent of changes in other lipids. The low-lipoprotein(a) group (baseline median 7 mg/dL) showed a small increase of median 2.6 mg/dL (week 24). Conclusions Marked increases in lipoprotein(a) after initiation of ART were mainly restricted to patients with high baseline levels. This may have clinical implications as patients with high lipoprotein(a) are at higher risk for myocardial infarction and stroke. [source]

Lipoprotein(a) levels in girls with premature adrenarche

JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 3 2008
Nesibe Andiran
Aim: Elevated lipoprotein(a) (Lp(a)) level is a risk factor for cardiovasculary disease (CVD). Women with polycystic ovary syndrome (PCOS) have higher Lp(a) and risk for CVD than controls. The girls with premature adrenarche (PA) were shown to share similar hormonal/metabolic properties with PCOS. We compared Lp(a) levels in PA, with healthy and PCOS girls. Methods: In total, 25 PA, 20 controls and 10 girls with PCOS were evaluated. Lp(a), lipid profiles and insulin, glucose, free testosterone, dehydroepiandrosterone sulfate (DHEAS) and androstenedione levels were measured. A family history about CVD was obtained. Results: The mean age of girls with PA, at time of the study, was 10.04 ± 1.53, control 9.83 ± 1.58 and PCOS was 16.58 ± 1.46 years. The median (range) of Lp(a) levels were 22.5 (3.50,99.90), 9.6 (3.33,32.40) and 21.2 (5.89,85.65) mg/dL in PA, control and PCOS groups, respectively (P > 0.05). The median Lp(a)'s were 14.5 (3.50,87.00) and 24.30 (6.20,99.90) mg/dL, in prepubertal (Tanner 1) and pubertal PA girls (Tanner 2,5), respectively (P > 0.05). The median Lp(a) of prepubertal peers was 8.7 (3.33,21.17), while that of pubertal ones was 15.4 (4.72,32.40) mg/dL (P > 0.05). There was no difference between Lp(a) levels of pre-pubertal PA girls and their peers; however, significant difference was found in Lp(a) levels in pubertal stages of PA and healthy peers (P < 0.05). The positive family history of CVD was 60% in PA; 55% and 80% in the control and PCOS groups, respectively, with no statistical difference. Lp(a) level was correlated with DHEAS (r = 0.386, P = 0.008) and free testosterone (r = 0.337, P = 0.022) levels positively. There was no significant correlation between Lp(a) and body mass index, fasting insulin and fasting glucose/insulin ratio. Conclusions: Lipoprotein(a) levels in pubertal girls with PA differ significantly from healthy peers. However, to clarify whether the girls with PA have an additional risk for CVD with respect to Lp(a), further follow-up studies with larger number of patients are necessary. [source]

ADH Genotype Does Not Modify the Effects of Alcohol on High-Density Lipoprotein

ALCOHOLISM, Issue 3 2003
John B. Whitfield
Background: Alcohol consumption has beneficial effects on mortality which are mainly due to reduction in cardiovascular disease. These are believed to be due, at least in part, to the increase in plasma high-density lipoprotein (HDL) which is associated with alcohol consumption. It has been proposed that ADH3 genotype modifies the relationships between alcohol intake and cardiovascular disease by altering the HDL response to alcohol. The aim of this paper was to test for effects of ADH2 and ADH3 genotypes on the response of HDL components to habitual alcohol consumption. Methods: Adult male and female subjects were genotyped for ADH2 and ADH3; and plasma HDL cholesterol, apolipoprotein A-I, and apolipoprotein A-II were measured. Nine hundred one subjects had both ADH2 and ADH3 genotypes and HDL cholesterol results, while 753 had both genotypes and all three lipid results. The effect of alcohol intake on the three measured HDL components, and a factor score derived from them, was estimated for each of the ADH2 and ADH3 genotype groups. Results: All the measured components of HDL increased with increasing alcohol consumption over the range of intakes studied, 0,4 drinks per day. There were no significant interactions between alcohol consumption and ADH2 or ADH3 genotypes. Conclusions: The concept that alcohol dehydrogenase genotype and alcohol metabolic rate modify the effects of alcohol on plasma HDL concentration is not supported by our results. [source]

Dual inverse effects of lipoprotein(a) on the dementia process in Japanese late-onset Alzheimer's disease

PSYCHOGERIATRICS, Issue 3 2004
Toshihiko IWAMOTO
Abstract Background: The role of lipoprotein metabolism in the dementia process has attracted increasing attention. It is universally accepted that apolipoprotein E4 (ApoE) is a risk factor for late-onset Alzheimer's disease, however, the role of lipoprotein(a) (Lp(a)) remains unclear. Therefore, we conducted the present study to clarify the association between Lp(a) and dementia. Methods: Lipoprotein(a) serum concentrations were examined in relation to ApoE phenotypes and periventricular lucency (PVL) on brain computed tomography in 150 patients with late-onset Alzheimer's disease (AD group), compared with 46 patients with vascular dementia (VaD group) and 150 controls without dementia. Results: The incidences of hypertension, hypercholesterolaemia, and severe PVL were significantly higher in the VaD group than in the AD group. The distributions of Lp(a) concentrations showed left-skewed deviation in each group, but we found the concentration of 40 mg/dL to be the best cut-off point to distinguish the frequency of Alzheimer's disease from that of the controls. Compared with the frequency of high Lp(a) concentrations of 40 mg/dL or more in the controls (16.7%), that in the AD group (10.0%) was significantly lower, while that in the VaD group (45.7%) was significantly higher. Separating the AD group according to the presence or absence of ApoE4, the same findings were recognized. However, severe PVL was more frequent in the AD group with high Lp(a) concentrations (53.3%) than in the AD group without high Lp(a) concentrations (7.4%) (P < 0.01). Conclusions: These findings suggest the possibility of dual inverse effects of Lp(a) on the occurrence of Japanese late-onset Alzheimer's disease, via suppression of Alzheimer's related processes and promotion of PVL formation presumably caused by ischemia. [source]

Coatings of Low-Density Lipoprotein and Synthetic Glycoconjugates as Substrata for Hepatocytes

ARTIFICIAL ORGANS, Issue 6 2009
Hirofumi Yura
Abstract Asialoglycoprotein (ASGP) receptors expressed on rat hepatocytes interact with glycoproteins containing galactose or N-acetylgalactosamine residues at the nonreducing termini of oligosaccharide chains to mediate endocytosis, and cholesterol transport protein with apolipoprotein B (LDL, low-density lipoprotein) in plasma interacts with LDL receptors and heparinoids in the extracellular matrix. We developed novel techniques to prepare galactose- and LDL-immobilized culture plates, using galactose-tagged polystyrene (galactose-carrying polystyrene [GalCPS]: N-p-vinylbenzyl-O-,-D-galactopyranosyl-[1,4]-D-gluconamide) and poly(2-acrylamide-2-methyl-1-propanesulfonate) (PAPS), respectively. Hepatocytes adhered well to plates coated with either GalCPS or LDL, and therefore the GalCPS- and LDL-coated plates were examined as specific substrata for culturing hepatocytes. These cultures promoted the formation of three-dimensional, multicellular aggregates with regulation of excess proliferation of non-parenchymal cells. Furthermore, the LDL coating resulted in higher albumin synthesis and an identical level of lactate dehydrogenase (LDH) compared with cells cultured on collagen- and GalCPS-coated plates. Thus, the two culture systems described here, and especially the LDL-coated plates, have potential for the development of a hybrid artificial liver. [source]

Cytokine Release and Serum Lipoprotein (a) Alterations During Hemodialysis

ARTIFICIAL ORGANS, Issue 5 2000
Helen A. Tzanatos
Abstract: It has been reported recently that a number of cytokines, mainly tumor necrosis factor , (TNF,), interleukin (IL)-1,, and IL-6, can alter lipid metabolism and produce hyperlipidemia. Studies in hemodialysis (HD) patients have demonstrated increased production of these cytokines during HD. In order to investigate any possible relationship between changes of cytokines and lipid concentrations during HD in the serum of 25 uremic patients on chronic HD using modified cellulose membranes, TNF,, IL-1,, IL-6, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein a (Lp[a]), and total proteins were measured immediately before (pre-HD) and after HD (post-HD), in one session. The post-HD values were corrected according to the hemoconcentration based on the changes in serum total proteins. Serum TNF, and IL-1, levels were significantly increased from 38.24 ± 17.85 pg/ml and 2.60 ± 3.64 pg/ml pre-HD to 48.86 ± 25.21 and 3.49 ± 4.08 pg/ml post-HD, p < 0.001 and p < 0.05 respectively. Also Lp(a) levels presented a statistically significant increase post-HD and were almost doubled (pre-HD: 15.41 mg/dl, to post-HD: 27.39 mg/dl, p < 0.05). Serum IL-6 as well as serum TC, TG, HDL-C, and LDL-C did not show any statistically significant alterations during HD. A significant positive correlation was detected between TNF, and Lp(a) values post-HD (r: 0.413, p: 0.04), but not between pre-HD values. No further relationship between serum cytokines and the other estimated lipid parameters was observed, either between pre- or post-HD values. Our results indicate that release of TNF, and IL-1, during HD have no effect on serum lipids concentration, except on Lp(a). It seems that the acute rise of this lipoprotein during hemodialysis may be related with the TNF, overproduction. [source]

Antiphospholipid antibodies and lipoprotein(a) in obese children

ACTA PAEDIATRICA, Issue 4 2009
Devis Pascut
Abstract Aim: Antiphospholipid (aPL) antibodies, Lipoprotein(a) [Lp(a)] and obesity are considered three independent risk factors for development of cardiovascular diseases. We investigate the presence of aPL antibodies and the Lp(a) concentration in 190 obese and 30 healthy children divided into prepubertal and pubertal, compared with healthy adults. Results: aPL antibodies were detected in 2.65% of prepubertal and in 2.59% of pubertal obese children. Considering results obtained by Lp(a) test, 4.4% of prepubertal and 5.2% of pubertal obese children and 17.5% of healthy adults were at risk for development of cardiovascular diseases. Conclusion: The presence of various prothrombotic risk factors increases the probability of developing thrombosis. Considering aPL antibodies there is no statistically significant difference among the different considered groups; therefore each category has the same risk factor. The Lp(a) distribution in adults is significantly different from the Lp(a) distribution in prepubertal (p = 0.012) and pubertal (p = 0.029) obese children. There is no significant difference among prepubertal subjects (p = 0.632) as well as pubertal subjects (p = 0.465), independently from the BMI. These results suggest the control of BMI in young population to avoid the presence of the obesity as another independent prothrombotic risk factor to be added to aPL and Lp(a) in the future adulthood. [source]

Epidemiological Association between Uric Acid Concentration in Plasma, Lipoprotein(a), and the Traditional Lipid Profile

CLINICAL CARDIOLOGY, Issue 2 2010
Giuseppe Lippi MD
Abstract Background Elevated levels of uric acid in serum (SUA) or plasma (PUA) are increasingly related to cardiovascular disease. It is unclear whether they are independent risk factors or simply markers, reflecting association with other traditional risk factors. Methods We retrospectively assessed results of a lipid profile, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, total cholesterol to HDL-C ratio (TC/HDL-C), the atherogenic index of plasma (AIP), and lipoprotein(a) (Lp[a]), in a large cohort of unselected adult outpatients. Results Hyperuricemic men displayed significantly increased values of triglycerides and AIP when compared with men with normal PUA levels. In hyperuricemic women, significant differences were observed for HDL-C, triglycerides, TC/HDL-C, and AIP compared with women with normal PUA levels. The percentage of patients with unfavorable values was statistically higher for triglycerides and AIP in hyperuricemic men; for HDL-C, triglycerides, TC/HDL-C, and AIP in hyperuricemic women. In multivariable linear regression analysis triglycerides, AIP, and TC/HDL-C were independently associated with PUA in women, whereas no significant association was observed in men. Conclusion PUA measurement might be advisable in patients to identify those at increased risk of cardiovascular disease (CVD) who might benefit from further triage and intervention. Copyright © 2010 Wiley Periodicals, Inc. [source]

Lipoprotein(a) was an independent predictor for major coronary events in treated hypertensive men

CLINICAL CARDIOLOGY, Issue 6 2002
Ph.D., Stefan Agewall M.D.
Abstract Background and Hypothesis: Lipoprotein(a) may play a part in the development of coronary heart disease. The purpose of this prospective study was to evaluate lipoprotein(a) as a predictor of major coronary events (fatal and nonfatal myocardial infarction and sudden death). Methods: This was a prospective study of 118 men, aged 56 to 77 years, with treated hypertension and at least one additional cardiovascular risk factor (hypercholesterolemia, diabetes mellitus, or smoking) were included in the study. Lipoprotein(a) was measured at entry and major coronary events were followed during follow-up. Results: The mean observation time was 3.0 years. Fourteen patients had a major coronary event during the follow-up period. Subjects with coronary heart disease (previous myocardial infarction, angina pectoris, or major electrocardiographic changes) at entry (n = 27) had significantly higher lipoprotein(a) levels than subjects without (n = 91) known coronary heart disease (p < 0.05). Lipoprotein(a) was a significant predictor for major coronary events (p = 0.033). Furthermore, when coronary disease at entry was included into the Cox regression analysis, lipoprotein(a) was an independent predictorfor major coronary events (p = 0.044). Conclusions: Among treated hypertensive men, lipoprotein(a) was an independent predictor of major coronary events. [source]

Lipoprotein(a) Is Related to the Extent of Lesions in the Coronary Vasculature and to Unstable Coronary Syndromes

CLINICAL CARDIOLOGY, Issue 12 2000
B.Sc., John D. Zampoulakis M.D.
Abstract Background: Lp(a) is a highly atherogenic particle with a prothrombotic effect. Until now its relation to the extent and severity of the atheromatic lesions had not been established by standard procedures. Hypothesis: This study examined the correlation of Lp(a) to the extent and severity of coronary artery disease (CAD) and its relation to unstable clinical events (not including sudden death). Methods: In 202 patients undergoing coronary angiography, plasma lipids were measured with the usual procedures and Lp(a) with the enzyme-linked immunosorbent assay. The extent of CAD was expressed in the number of diseased vessels and its severity in terms of the severity coefficient and the obstruction coefficient. Results: A very strong relationship between LP(a) and the number of diseased vessels (p = 0.0007) signifying diffuse atherosclerosis, but no relation with the severity of the lesions, was found. However, it was the only lipid that correlated significantly with the number of totally occluded vessels (p = 0.0003). The thrombogenic ability of Lp(a) was manifested by increased incidence of myocardial infarction and unstable angina episodes in patients with elevated Lp(a) (p = 0.0157). Conclusion: Elevated Lp(a) predisposes to the extent of CAD and total occlusions but not to the severity of lesions. Patients with increased Lp(a) levels and unstable angina are at increased danger of suffering myocardial infarction. Thus, Lp(a) may predispose to plaque destabilization and thrombosis of noncritical lesions. [source]

,Lipoproteins, glycoxidation and diabetic angiopathy'

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2004
Alicia J. Jenkins
Abstract The chronic vascular complications of diabetes (nephropathy, retinopathy and accelerated atherosclerosis) are a major cause of morbidity and premature mortality. In spite of the more widespread availability of intensive diabetes management, approximately one in three people with diabetes develop aggressive complications and over 70% die of atherosclerosis-related diseases. Genetic and acquired factors are likely to be contributory. Potential mediators of vascular damage may include the interrelated processes of lipoprotein abnormalities, glycation, oxidation and endothelial dysfunction. Lipoprotein abnormalities encompass alterations in lipid concentrations, lipoprotein composition and subclass distribution and lipoprotein-related enzymes. Nonenzymatic glycation and oxidative damage to lipoproteins, other proteins and to vascular structures may also be deleterious. As atherosclerosis is a chronic condition commencing in youth, and because clinical events may be silent in diabetes, surrogate measures of vascular disease are important for early identification of diabetic patients with or at high risk of vascular damage, and for monitoring efficacy of interventions. The increasing array of biochemical assays for markers and mediators of vascular damage, noninvasive measures of vascular health, and therapeutic options should enable a reduction in the excessive personal and economic burden of vascular disease in type 1 and type 2 diabetes. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Pecan Effects on Serum Lipoproteins and Dietary Intakes of Hyperlipidemic Individuals Consuming Self-Selected Diets

FAMILY & CONSUMER SCIENCES RESEARCH JOURNAL, Issue 3 2005
Wanda A. Eastman
Pecan-supplemented diets were studied in 17 hyperlipidemic individuals who were randomly assigned to pecan (6 women, 2 men, age 46±6 years [mean±SD]) or control (7 women, 2 men, age 53±10 years). The pecan group consumed 68g of pecans/day for 8 weeks. Total fat, monounsaturated fat, and polyunsaturated fat intakes were significantly higher in the pecan group. LDL cholesterol was lowered in the pecan group from 152±21 mg/dL at entrance to 136±22 at Week 4 but was 153±33 by Week 8. LDL cholesterol was significantly lower in the pecan group than controls at Week 4 (136±22 mg/dL versus 173±60). Total cholesterol in the pecan group was 233±19 mg/dL at entrance and 221±18 by Week 4 but was 232±35 by Week 8. Total cholesterol was significantly lower in the pecan group (221±18 mg/dL) than controls (257±60) at Week 4. Pecans in diets of hyperlipidemic individuals did not have sustained serum lipid lowering. [source]

Amelioration of Cadmium-Induced Oxidative Stress, Impairment in Lipids and Plasma Lipoproteins by the Combined Treatment with Quercetin and ,-Tocopherol in Rats

JOURNAL OF FOOD SCIENCE, Issue 7 2010
S. Milton Prabu
Abstract:, Cadmium (Cd) exposure results in numerous pathological consequences including oxidative stress and dyslipidemia. The present study was designed to investigate the efficacy of combined treatment with quercetin (QE) and ,-tocopherol (AT) against Cd-induced oxidative stress and alterations in lipids and lipoproteins in the plasma and liver of rats. Oral administration of Cd (5 mg/kg bw/d) for 4 wk has shown a significant (P < 0.05) increase in thiobarbituric acid reactive substances (TBARS), lipid hydro peroxides (LOOH), total cholesterol, low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), free fatty acids (FFA), phospholipids (PL), triglycerides (TGs), and the activity of hydroxyl-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) in plasma with a significant (P > 0.05) reduction in the levels of reduced glutathione (GSH), high density lipoprotein cholesterol (HDL-C), and the activity of lecithin cholesterol acyl transferase (LCAT) in plasma. In addition, the levels of hepatic thiobarbituric acid reactive substances (TBARS), LOOH, conjugated dienes (CD), protein carbonyls (PC), and the activity of HMG-CoA reductase, levels of cholesterol, FFA, and TGs were significantly (P > 0.05) increased and the level of PL is significantly (P > 0.05) decreased along with the decreased activity of LCAT in the liver of Cd-treated rats. Oral supplementation with QE (50 mg/kg bw/d) and AT (50 mg/kg bw/d) for 4 wk in Cd intoxicated rats significantly (P > 0.05) has reduced the plasma levels of TBARS, LOOH, GSH, cholesterol, FFA, TGs, VLDL-C, LDL-C, and the activity of HMG-CoA and significantly (P > 0.05) has increased the activity of LCAT and the plasma levels of HDL-C. The oral supplementation also significantly (P > 0.05) has reduced the hepatic oxidative stress markers, cholesterol, TGs, FFA, and significantly (P > 0.05) has increased the LCAT activity and the PL in liver. Our results indicate that the combined treatment with QE and AT has normalized all the previously mentioned biochemical parameters in Cd-intoxicated rats than the individual treatments. The combined treatment has provided remarkable protection against Cd-induced oxidative stress and alterations in lipid metabolism and, thereby, reduced the Cd-mediated cardiovascular diseases. [source]

Investigating lipoprotein biogenesis and function in the model Gram-positive bacterium Streptomyces coelicolor

MOLECULAR MICROBIOLOGY, Issue 4 2010
Benjamin J. Thompson
Summary Lipoproteins are a distinct class of bacterial membrane proteins that are translocated across the cytoplasmic membrane primarily by the Sec general secretory pathway and then lipidated on a conserved cysteine by the enzyme lipoprotein diacylglycerol transferase (Lgt). The signal peptide is cleaved by lipoprotein signal peptidase (Lsp) to leave the lipid-modified cysteine at the N-terminus of the mature lipoprotein. In all Gram-positive bacteria tested to date this pathway is non-essential and the lipid attaches the protein to the outer leaflet of the cytoplasmic membrane. Here we identify lipoproteins in the model Gram-positive bacterium Streptomyces coelicolor using bioinformatics coupled with proteomic and downstream analysis. We report that Streptomyces species translocate large numbers of lipoproteins out via the Tat (twin arginine translocase) pathway and we present evidence that lipoprotein biogenesis might be an essential pathway in S. coelicolor. This is the first analysis of lipoproteins and lipoprotein biogenesis in Streptomyces and provides the first evidence that lipoprotein biogenesis could be essential in a Gram-positive bacterium. This report also provides the first experimental evidence that Tat plays a major role in the translocation of lipoproteins in a specific bacterium. [source]

High-density Lipoproteins: Effects of Alcohol, Estrogen, and Phytoestrogens

NUTRITION REVIEWS, Issue 1 2002
Stefania Lamon-Fava MD
Plasma high-density lipoproteins (HDL) play an important role in the reverse cholesterol transport pathway. Factors affecting plasma HDL levels may be important, therefore, in the prevention of cardiovascular disease. Among the lifestyle and environmental factors that have been shown to increase HDL cholesterol are moderate alcohol intake and estrogen administration. Phytoestrogens, molecules of plant origin that resemble estrogen and act as weak estrogens, do not have a clear effect on HDL cholesterol. The molecular mechanisms of action of alcohol, estrogen, and phytoestrogens on HDL are under investigation. [source]

Analysis of Lipoproteins and Body Mass Index in Professional Football Players

PREVENTIVE CARDIOLOGY, Issue 3 2001
Joseph P. Garry MD
Exercise is known to improve lipoprotein levels, whereas an elevated body mass index (BMI) is associated with less favorable lipoprotein levels. To date, there have been no reports of lipid analyses in elite athletes who also have BMIs in ranges considered unhealthful. The purpose of this study was to evaluate the lipid-lipoprotein profiles in a group of professional football players and to determine what association exists between these profiles and the players' BMIs. An observational study was conducted of 70 professional football players from one National Football League team. Measurements included BMI (kg·m,2), and fasting serum lipid analysis. BMI and position played were found to correlate (p<0.001), with linemen having the highest mean BMI, 38.1 kg·m,2. Comparing mean lipid values among BMI categories demonstrated lower high-density lipoprotein cholesterol levels (p<0.01), higher triglycerides (p<0.05), and higher total cholesterol/high-density lipoprotein cholesterol ratios (p<0.001) with an increasing BMI. Among the professional football players studied, a lower BMI was associated with a more favorable lipid-lipoprotein profile. Among the elite athletes in this study with the highest BMIs, exercise may not confer the same protective benefits on cardiovascular risk as it does in those athletes with normal BMIs. [source]

Apolipoproteins and , Amyloid Transport Pathway

PSYCHOGERIATRICS, Issue 3 2002
Kouzin Kamino
Abstract: Cholesterol metabolism has been viewed as an important step in the development of Alzheimer's disease, since it was shown that the ,4 allele of apolipoprotein E (APOE) gene is a genetic risk and modifies age-at-onset of Alzheimer's disease. Although the knowledge of the effect of cholesterol in the neuronal cell has been recently accumulated, the link between systemic and brain cholesterol metabolism remains to be elucidated. Lipoproteins in cerebrospinal fluid (CSF) are fractionated only to high-density lipoprotein (HDL), and contain apolipoprotein (apo) A-I, E, A-II, and J. Whereas apoE is produced in the brain, apoA-I and apoA-II in cerebrospinal fluid, the major components of plasma HDL cholesterol, originate from plasma. Plasma HDL is thought to act in reverse cholesterol transport, and in vitro experiments indicated that these apolipoproteins and albumin show a high affinity binding to , amyloid. In patients with Alzheimer's disease, plasma apoA-I and apoA-II levels are significantly decreased, which is possibly related to the deposition of , amyloid in the brain, and to the , amyloid transport pathway. [source]

DALI Apheresis in Hyperlipidemic Patients: Biocompatibility, Efficacy, and Selectivity of Direct Adsorption of Lipoproteins from Whole Blood

ARTIFICIAL ORGANS, Issue 2 2000
T. Bosch
Abstract: Recently, the first apheresis technique for direct adsorption of low-density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] from whole blood (DALI) was developed that does not require a prior plasma separation. That markedly simplifies the extracorporeal circuit. The aim of the present study was to test the acute biocompatibility, efficacy, and selectivity of DALI apheresis. In a prospective clinical study, 6 hypercholesterolemic patients suffering from angiographically proven atherosclerosis were treated 4 times each by DALI. 1.3 patient blood volumes were treated per session at blood flow rates of 60,80 ml/min using 750 or 1,000 ml of polyacrylate/polyacrylamide adsorber gel. The anticoagulation consisted of an initial heparin bolus followed by a citrate infusion. The sessions were clinically essentially uneventful. Mean corrected reductions of lipoproteins amounted to 65% for LDL-cholesterol, 54% for Lp(a), 28% for triglycerides, 1% for HDL-cholesterol, and 8% for fibrinogen. The selectivity of lipoprotein removal was high. Cell counts remained virtually unchanged and no signs of hemolysis or clotting were detected. Cell activation parameters elastase, ,-thromboglobulin, interleukin-1,, and IL-6 showed no significant increase. Complement activation was negligible. There was significant, but clinically asymptomatic, bradykinin activation in the adsorber with mean maxima of 12,000 pg/ml in the efferent line at 1,000 ml of treated blood volume. In conclusion, DALI proved to be safe, selective, and efficient for the adsorption of LDL-C and Lp(a), which simplifies substantially the extracorporeal therapy in hypercholesterolemic patients. [source]

Fate of fatty acids at rest and during exercise: regulatory mechanisms

ACTA PHYSIOLOGICA, Issue 4 2003
M. D. Jensen
Abstract Fatty acids are a major fuel source for humans both at rest and during exercise. Plasma free fatty acids (FFA), although present only in micromolar concentrations, are the major circulating lipid fuel. FFA availability can increase two- to four-fold with moderate intensity exercise. Other potential sources of fatty acids include circulating very low-density lipoprotein (VLDL) triglycerides (TGs) (,1/5 the fuel availability of FFA) and intramyocellular TGs (,2 mmol kg,1 muscle). At rest ,40% of systemic FFA uptake occurs in the splanchnic bed and uptake in legs is ,15,20%. During leg exercise the uptake of FFA in leg tissue increases to 30,60% of systemic uptake and splanchnic uptake decreases to 15%. The fate of VLDL TG fatty acids has not been adequately studied. Intramyocellular TG hydrolysis increases during exercise, but the factors that regulate this response are not clear. The fact that contraction of isolated muscles can stimulate the hydrolysis and oxidation of intramyocellular TGs (in the absence of hormonal or neural input) suggests an intracellular regulation of this process. Additional regulation from changes in catecholamines and insulin may also occur. During moderate intensity exercise circulating FFA and intramyocellular TG provide roughly equal portions of fatty acids for oxidation. In addition to endurance training, dietary factors have been shown to modulate the fatty acid oxidation response to exercise. Much remains to be learned about fatty acid trafficking during exercise. What role do VLDL TG play? How is the oxidation of intramyocellular TGs regulated? Techniques to address these questions in humans are only now becoming available. [source]

Depression and the metabolic syndrome: gender-dependent associations

DEPRESSION AND ANXIETY, Issue 8 2008
Sharon Toker Ph.D.
Abstract This study was designed to test the extent to which depressive symptoms are associated with the presence of the metabolic syndrome (MS) and each of its components, and whether these relationships are gender dependent. Participants were apparently healthy employed men (N=2,355) and women (N=1,525) who underwent a routine health check between the years 2003 and 2005. We used logistic regression analysis, predicting the MS by depressive symptoms, as assessed by the Patient Health Questionnaire, and the following control variables: age, education, smoking status, physical exercise, anxiety, and burnout. As hypothesized, we found that depression among women, but not men, was associated with a 1.94-fold risk of having the MS, and with an elevated risk of having two of its five components: elevated waist circumference (odds ratio, OR=2.23) and elevated glucose levels (OR=2.44). In addition, a positive trend was observed toward an association with the other three components: low high-density lipoprotein, hypertension, and elevated triglycerides. Among men depression was associated with elevated waist circumference only (OR=1.77). These findings suggest that especially among women, the association between depression and cardiovascular diseases might be linked to metabolic processes. If replicated in longitudinal studies, these findings may have important health-care policy implications with regard to depression management interventions. Depression and Anxiety 0:1,9, 2007. © 2007 Wiley-Liss, Inc. [source]

Long-term use of the ketogenic diet in the treatment of epilepsy

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 12 2006
Darcy K Groesbeck BS
Long-term outcomes of the ketogenic diet in the treatment of epilepsy have not previously been reported. A retrospective chart review of children treated with the ketogenic diet for more than 6 years at the Johns Hopkins Hospital was performed. The response was documented at clinic visits and by telephone contacts; laboratory studies were obtained approximately every 6 to 12 months. Satisfaction and tolerability were assessed by means of a brief parental telephone questionnaire. In all, 28 patients (15 males, 13 females), currently aged 7 to 23 years, were identified. The median baseline seizure frequency per week at diet onset was 630 (range 1,1400). Diet duration ranged from 6 to 12 years; 19 remain on the diet currently. After 6 years or more, 24 children experienced a more than 90% decrease in seizures, and 22 parents reported satisfaction with the diet's efficacy. Ten children were at less than the 10th centile for height at diet initiation; this number increased to 23 at the most recent follow-up (p=0.001). Kidney stones occurred in seven children and skeletal fractures in six. After 6 years or more the mean cholesterol level was 201mg/dl, high-density lipoprotein was 54mg/dl, low-density lipoprotein was 129mg/dl, and triglycerides were 97mg/dl. Efficacy and overall tolerability for children are maintained after prolonged use of the ketogenic diet. However, side effects, such as slowed growth, kidney stones, and fractures, should be monitored closely. [source]

Reverse cholesterol transport in type 2 diabetes mellitus

DIABETES OBESITY & METABOLISM, Issue 6 2009
K. C. B. Tan
High-density lipoprotein (HDL) plays an important protective role against atherosclerosis, and the anti-atherogenic properties of HDL include the promotion of cellular cholesterol efflux and reverse cholesterol transport (RCT), as well as antioxidant, anti-inflammatory and anticoagulant effects. RCT is a complex pathway, which transports cholesterol from peripheral cells and tissues to the liver for its metabolism and biliary excretion. The major steps in the RCT pathway include the efflux of free cholesterol mediated by cholesterol transporters from cells to the main extracellular acceptor HDL, the conversion of free cholesterol to cholesteryl esters and the subsequent removal of cholesteryl ester in HDL by the liver. The efficiency of RCT is influenced by the mobilization of cellular lipids for efflux and the intravascular remodelling and kinetics of HDL metabolism. Despite the increased cardiovascular risk in people with type 2 diabetes, current knowledge on RCT in diabetes is limited. In this article, abnormalities in RCT in type 2 diabetes mellitus and therapeutic strategies targeting HDL and RCT will be reviewed. [source]

Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulation

DIABETES OBESITY & METABOLISM, Issue 11 2008
R. R Ortiz-Andrade
Aim:, The present investigation was designed to determine the in vivo antidiabetic effect of naringenin (NG) in normoglycaemic and diabetic rat models through blood glucose (GLU) measurements following acute and subchronic time periods. Possible modes of action of NG were investigated and its acute toxicity determined. Methods:, Normoglycaemic and non-insulin-dependent diabetes mellitus (NIDDM) rat models were treated for acute and subchronic (5 days) time periods with 50 mg/kg/day of NG. Blood biochemical profiles were determined after 5 days of the treatment in normoglycaemic and NIDDM rats using commercial kits for GLU, triglycerides (TG), total cholesterol (CHOL) and high-density lipoprotein (HDL). In order to elucidate its antidiabetic mode of action, NG was administered intragastrically and an oral glucose tolerance test performed using GLU and sucrose (2 g/kg) as substrates. The inhibitory effect of a single concentration of NG (10 ,M) on 11,-hydroxysteroid dehydrogenase type 1 (11,-HSD1) activity in vitro was determined. Finally, the preclinical safety and tolerability of NG was determined by toxicological evaluation in mice and rats using Organization for Economic Cooperation and Development (OECD) protocols. Results:, Intragastrically administered NG (50 mg/kg) induced a significant decrease in plasma GLU in normoglycaemic and NIDDM rat models (p < 0.05) following acute and subchronic time periods. After 5 days of administration, NG produced significant diminished blood GLU and TG levels in streptozotocin,nicotinamide,induced diabetic rats. The administration of NG to normal rats significantly increased the levels of TG, CHOL and HDL (p < 0.05). NG (5 and 50 mg/kg) induced a total suppression in the increase of plasma GLU levels after administration of substrates (p < 0.01), but NG did not produce inhibition of ,-glucosidase activity in vitro. However, NG (10 ,M) was shown to inhibit 11,-HSD1 activity by 39.49% in a cellular enzyme assay. Finally, NG showed a Medium Lethal Dose LD50 > 5000 mg/kg and ranking at level five based on OECD protocols. Conclusion:, Our findings suggest that NG may exert its antidiabetic effect by extra-pancreatic action and by suppressing carbohydrate absorption from intestine, thereby reducing the postprandial increase in blood GLU levels. [source]

How to identify patients with vulnerable plaques

DIABETES OBESITY & METABOLISM, Issue 10 2008
Salim S. Virani
Multiple strategies are available for clinicians to identify patients at high risk for cardiovascular events. Two commonly discussed strategies are the identification of vulnerable plaques and the identification of vulnerable patients. The strategy of identifying vulnerable patients is less invasive, easy to implement and not restricted primarily to one vascular bed (e.g. coronary or cerebral). This review discusses the utility as well as the limitations of global risk assessment tools to identify such patients. The utility of biomarkers [C-reactive protein, lipoprotein-associated phospholipase A2 and lipoprotein(a)] and non-invasive measures of atherosclerosis burden (coronary artery calcium scores, carotid intima,media thickness and ankle,brachial index) in identifying patients at high risk for cardiovascular events are also discussed. [source]

Effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects

DIABETES OBESITY & METABOLISM, Issue 3 2006
M. González-Ortiz
Aim:, To identify the effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) in single administration on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects. Methods:, A randomized, single-blind, cross-over, clinical trial was carried out in 14 young, healthy, non-obese, volunteers. A basal metabolic profile, which included glucose level, insulin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinine, and uric acid, was measured. Subjects received a single administration of 300 kcal, gauged with water at 350 ml, of each of the following (at least 3 days apart): glucose 75 g, polymeric supplement (Ensure high calcium) 315 ml or Glucerna SR 323 ml. At the beginning of each administration and 30, 60, 90 and 120 min later, glucose and insulin concentrations were measured. Areas under the curve of glucose and insulin were calculated. First-phase and total insulin secretions and insulin sensitivity were also estimated. Results:, Glucose level at 120 min was significantly lower after receiving Ensure high calcium or Glucerna SR. Administration of Glucerna SR resulted in a significant reduction in the areas under the curve of glucose and insulin, as well as in total insulin secretion with a tendency to be lower in their first phase. Insulin sensitivity was increased. Conclusions:, A single administration of Glucerna SR to healthy subjects decreased the postprandial glucose and insulin states, as well as the insulin secretion; insulin sensitivity increased. [source]

Lipids and lipoprotein(a) concentrations in Pakistani patients with type 2 diabetes mellitus

DIABETES OBESITY & METABOLISM, Issue 5 2004
S. S. Habib
Aim:, The aim of the present study was to analyze serum lipoprotein(a) [Lp(a)] levels in Pakistani patients with type 2 diabetes mellitus (DM) and to find correlations between clinical characteristics and dyslipidaemias in these patients. Methods:, Fasting blood samples were analyzed for Lp(a), total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), glucose and glycosylated haemoglobin (HbA1c) in 68 Pakistani patients with type 2 DM and 40 non-diabetic healthy control subjects. Results:, Lp(a) levels were significantly raised in diabetics as compared to the control group. No correlation of Lp(a) was seen with age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting glucose. There was a positive correlation of BMI to SBP and DBP. There was a significant positive correlation between Lp(a) and total cholesterol and LDL-c. No correlation of Lp(a) was observed with HDL-c, triglycerides and glycosylated haemoglobin (HbA1c). Conclusion:, The present study led us to conclude that serum Lp(a) levels are significantly raised in type 2 DM and have a positive correlation with serum total and LDL-c levels. [source]

Hormonal influences on lipoprotein(a) metabolism

DIABETES OBESITY & METABOLISM, Issue 3 2002
R. W. C. Pang
First page of article [source]