Biomedical subjects

M W Baumstark

Publications and source records attributed to M W Baumstark.

At least 19 recordsLinked to original sources

PubMed2004

Lipoprotein phenotype and adhesion molecules correlate with diurnal triglyceride profiles in patients with coronary artery disease.

BACKGROUND AND AIM: To assess the relationships between different diurnal triglyceride (TG) profiles (p) and the atherogenicity of the lipoprotein phenotype and adhesion molecule concentrations in patients with coronary artery disease (CAD). METHODS AND RESULTS: Repeated measurements of fasting TG and TGp were made in 29 CAD patients; fasting cholesterol levels (total-C, VLDL, LDL, HDL and small dense LDL) and soluble cell adhesion molecules (sCAM) (ICAM-1 and E-selectin) were measured once. Three different TGps were defined: fasting (137.0 +/- 60.7 mg/dL) and all other TG levels <200 mg/dL (LL; n=7); a fasting TG level <200 mg/dL (147.0 +/- 49.9 mg/dL) and maximum TG levels >200 mg/dL (LH; n=13); and both fasting (225.1+/-76.2 mg/dL) and maximum TG levels >200 mg/dL (HH; n=9). We then analysed the associations between the TGp types and the lipoprotein phenotype and CAMs. LL had significantly lower values than LH (p<0.05 for all parameters except sE-selectin) and HH (p<0.05 for all parameters) of VLDL (11.2 +/- 5.8, 18.8 +/- 9.4, 28.1 +/- 8.8 mg/dL), LDL-5 (11.6 +/- 3.3, 16.4 +/- 4.5, 22.1 +/-7.9 mg/dl) and LDL-6 (12.0 +/- 3.2, 17.0 +/- 5.7, 25.7 +/- 9.6 mg/dL), sICAM-1 (209.4 +/- 30.3, 267.5 +/- 60.6, 273.4 +/- 59.1 ng/dL) and sE-selectin (25.1 +/- 17.6, 35.5 +/- 11.5, 48.5 +/- 20.2 ng/dL). CONCLUSION: Although the differences in fasting TG levels between the LL and LH groups were not significantly different, LH had a more atherogenic lipoprotein phenotype and higher concentrations of adhesion molecules. TGp measurements seem to be suitable for identifying CAD patients with an unfavourable diurnal TG and atherosclerosis-prone lipoprotein metabolism.

Aged↗

PubMed2004

Qualitative effect of fenofibrate and quantitative effect of atorvastatin on LDL profile in combined hyperlipidemia with dense LDL.

INTRODUCTION: The association of elevated plasma triglyceride concentrations, decreased HDL-cholesterol, and dense LDL (dLDL) is referred to as the atherogenic lipoprotein phenotype. dLDL particularly plays a role in the metabolic syndrome and type 2 diabetes and may be one of the factors responsible for the increased risk for coronary artery disease in these patients. The effect of fenofibrate and atorvastatin on the LDL subfraction profile in patients with combined hyperlipidemia and a preponderance of dLDL was studied in a sequential design. METHODS: Six male patients with combined hyperlipidemia and dLDL received 160 mg/die supra-bioavailable fenofibrate. After a washout phase of 8 weeks all patients received 10 mg/die atorvastatin for another 8 weeks. At baseline, after fenofibrate, and after atorvastatin treatment LDL subfractions were analyzed by equilibrium density gradient ultracentrifugation. RESULTS: Treatment with atorvastatin and fenofibrate reduced serum cholesterol by 30 % and 21 % (p = 0.046) (p-values for differences between treatment groups), triglycerides by 32 % and 45 %, LDL cholesterol by 28 % and 16 %, and increased HDL cholesterol by 3 % and 6 %, respectively. Atorvastatin and fenofibrate treatment resulted in the following changes of apoB and LDL subfractions: LDL-1 (1.019 - 1.031 kg/L) - 31 % and + 15 % (p = 0.028); LDL-2 (1.031 - 1.034 kg/L) - 14 % and + 57 % (p = 0.028); LDL-3 (1.034 - 1.037 kg/L) - 20 % and + 30 % (p = 0.028); LDL-4 (1.037 - 1.040 kg/L) - 25 % and - 6 %; LDL-5 (1.040 - 1.044 kg/L) - 29 % and - 38 %; and LDL-6 (1.044 - 1.063 kg/L) - 39 % and - 55 % (p = 0.028). As a consequence, fenofibrate reduced LDL density significantly (p = 0.028 versus atorvastatin). CONCLUSIONS: Atorvastatin decreased all LDL-subfractions to a similar extent (quantitative effect) whereas fenofibrate reduced predominantly dLDL and changed the LDL profile towards medium dense LDL-particles (qualitative effect). Since medium dense LDL have a higher affinity to the LDL-receptor fenofibrate may have a higher antiatherogenic potential than assessed by the reduction of total LDL-cholesterol and triglycerides alone.

Adult↗

PubMed2004

Inhibition of HMG-CoA reductase with cerivastatin lowers dense low density lipoproteins in patients with elevated fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus.

OBJECTIVE: While 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors effectively decrease LDL cholesterol, it remains controversial whether these agents also lower dense LDL, which are considered particularly atherogenic. METHODS: We examined the effects of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin on lipids, lipoproteins, and apolipoproteins in 69 patients with elevated fasting glucose, impaired glucose tolerance, or type 2 diabetes, combined hyperlipoproteinemia and increased concentrations of dense LDL (apo B in LDL-5 plus LDL-6 > 25 mg/dl). The study was a multicenter, double-blind, randomized, parallel-group comparison of cerivastatin at 0.4 mg daily for 12 weeks (n = 34) and placebo (n = 35). RESULTS: Cerivastatin significantly reduced cholesterol (- 20 %, p < 0.001), IDL cholesterol - 37 %, p < 0.001), LDL cholesterol (- 26 %, p < 0.001), apolipoprotein B (- 25 %, p < 0.001), triglycerides (- 12 %, p < 0.05), and raised HDL cholesterol (+ 7.5 %, p < 0.05) and apolipoprotein AI (+ 7.2 %, p < 0.05). Cerivastatin signficantly lowered apolipoprotein B in all LDL subfractions (- 21 to - 28 %, p < 0.05). Absolute changes were greatest in dense LDL and the change in dense LDL made the largest contribution to the change of total LDL. The change of dense LDL was highly correlated with baseline values. There was no consistent relationship between the effect of cerivastatin on triglycerides and the decrease of dense LDL. CONCLUSIONS: The HMG CoA reductase inhibitor cerivastatin lowers total and LDL cholesterol and the concentration of dense LDL in patients with elevated fasting glucose, impaired glucose tolerance or type 2 diabetes.

Adult↗

PubMed2003

Cardiorespiratory fitness modifies the association between dietary fat intake and plasma fatty acids.

OBJECTIVES: To investigate the relation between (1) cardiorespiratory fitness and plasma saturated, monounsaturated and polyunsaturated fatty acids and (2) the interactions between cardiorespiratory fitness, dietary fat intake and plasma fatty acid composition. DESIGN: Cross-sectional analysis. SETTING AND SUBJECTS: The subjects were randomly selected, 127 middle-aged Finnish men participating in the DNASCO exercise intervention study. INTERVENTIONS: Cardiorespiratory fitness was determined spiroergometrically, dietary intake of macro- and micronutrients by 4-day food records and plasma fatty acids by gas chromatography. The subjects were divided into tertiles of aerobic fitness. RESULTS: Differences between fitness tertiles were not observed for dietary intake of total fat, and saturated, monounsaturated or polyunsaturated fatty acids (percent of total energy). In contrast, plasma saturated fatty acids were significantly lower (P <0.01) and polyunsaturated fatty acids significantly higher (P <0.05) in the highest fitness tertile compared to the lowest tertile. Dietary saturated fat intake was positively associated with plasma saturated fatty acids (r=0.342; P <0.05) and inversely with plasma polyunsaturated fatty acids (r=-0.453; P <0.01) only in the lowest fitness tertile. In addition, a positive correlation between body mass index and plasma saturated fatty acids (r=0.516; P <0.01) as well as a negative correlation between body mass index and plasma polyunsaturated fatty acids (r=-0.516; P <0.01) was observed in the lowest tertile solely. CONCLUSION: Different levels in cardiorespiratory fitness are associated with different levels in plasma saturated and polyunsaturated fatty acids and lead to modifications in the association between dietary and plasma fatty acids. These findings can perhaps be explained by a reduced hepatic fatty acid and lipoprotein synthesis as well as by an enhanced muscular lipid utilization, which are commonly seen in those who are physically active and who exhibit a higher level of fitness.

Chromatography, Gas↗

PubMed2001

Fluvastatin lowers atherogenic dense low-density lipoproteins in postmenopausal women with the atherogenic lipoprotein phenotype.

BACKGROUND: Although HMG-CoA reductase inhibitors (HMGRIs) are effective lipid-lowering agents, it remains controversial whether these agents also lower dense LDL (dLDL), a predominance of which is considered to contribute to the atherogenicity of the metabolic syndrome. METHODS AND RESULTS: In a multicenter, double-blind, randomized, placebo-controlled study, we determined the effect of the HMGRI fluvastatin on lipids, apolipoproteins, and LDL subfractions (by equilibrium density gradient ultracentrifugation). A total of 52 postmenopausal women with combined hyperlipidemia and increased dLDL were treated with either fluvastatin 40 mg/d (n=35) or placebo (n=17). After 12 weeks' treatment, significant reductions (P<0.001) in total cholesterol (-19%), IDL cholesterol (-35%), LDL cholesterol (-23%), apolipoprotein B (-21%), and apolipoprotein B in dLDL (-42%) were apparent among fluvastatin recipients. No significant changes in triglycerides or HDL cholesterol were observed. The effect of fluvastatin on dLDL was correlated with baseline values. There was no consistent relationship, however, between the effect of fluvastatin on triglycerides and the decrease in dLDL. CONCLUSIONS: Fluvastatin lowers total and LDL cholesterol and the concentration of dLDL. This profile may contribute to an antiatherogenic effect for fluvastatin that is greater than expected on the basis of changes in lipids and apolipoproteins.

Anticholesteremic Agents↗

PubMed2001

Low-resolution data analysis for low-density lipoprotein particle.

The knowledge of the molecular structure of LDL, a large lipoprotein complex, is of great interest for medical investigations. Currently available LDL crystals do not diffract to high resolution and do not allow the application of standard crystallographic techniques. Additional difficulties arise because of a very dense crystal packing and the presence of several components with quite different mean densities. Several ab initio phasing methods previously reported by the authors have been successfully applied to find a crystallographic image of LDL at a resolution of 27 A. The most promising results have been obtained using direct phasing with a connectivity analysis of the electron-density maps. The current image makes it possible to discern a single particle covered by a layer of relatively high density that is asymmetrically distributed on the particle surface. It shows a partition of high and low densities inside the particle and, in particular, strips of varying density in the lipid core.

Crystallography, X-Ray↗

PubMed2000

Lipoproteins and free plasma catecholamines in spinal cord injured men with different injury levels.

Persons with spinal cord injury (SCI) are especially prone to atherogenesis. This is partly explained by an unfavourable lipoprotein profile in these individuals. The impairment of the sympathetic nervous system, and the fact that SCI subjects are subject to extreme physical inactivity, may have an influence on their lipid profile and lipoprotein(a) concentration. We made a detailed investigation of the lipid profile as well as serum levels of adrenaline and noradrenaline in 80 men with SCI ranging from tetraplegia to low paraplegia and in 16 control subjects. The lipid profile of tetraplegics was characterized by elevated very low-density lipoprotein cholesterol and triglyceride levels and reduced high-density lipoprotein levels. In contrast, paraplegics had significantly higher low-density lipoprotein and total cholesterol levels. Tetraplegics had lower and the low-lesion paraplegics had higher adrenaline and noradrenaline levels than the high-lesion paraplegics and the control subjects. High-lesion SCI subjects also showed an extreme reduction in VO2max. The lipoprotein profile was dependent on the injury level and serum catecholamine concentrations. The lower the noradrenaline values, the lower the high-density lipoprotein cholesterol. The low-density lipoprotein also correlated to catecholamines and particularly adrenaline values. Despite the correlation between lipoprotein(a) and adrenaline, no significant differences in lipoprotein(a) were found within SCI individuals as well as between SCI individuals and control subjects, indicating the predominantly genetic determination of lipoprotein(a) and thus the cardiovascular risk. Different serum catecholamine levels due to impairment of sympathetic nervous system and VO2max levels were observed in SCI subjects. This was associated with a higher lipid risk profile for cardiovascular diseases; however, the risk profile is dependent on the lesion level.

Adult↗

PubMed2000

Low density lipoprotein (LDL) subfractions during pregnancy: accumulation of buoyant LDL with advancing gestation.

Pregnancy is accompanied by changes in the maternal lipoprotein metabolism that may serve to satisfy the nutritional demands of the fetus. In this study lipoprotein metabolism was investigated in 23 women during normal pregnancy in the first, second, and third trimesters and in 15 healthy nonpregnant women with regular menstrual cycles. Lipid and apolipoprotein concentrations were measured in total plasma, very low density, intermediate density, low density (LDL), and high density lipoproteins, and in each of six LDL subfractions. During early pregnancy, triglycerides, and dense LDL were higher than in the nonpregnant state. With advancing gestation, triglycerides increased and the distribution of apolipoprotein B-100-containing lipoproteins became increasingly dominated by the accumulation of very low density and intermediate density lipoproteins and buoyant, triglyceride-rich LDL. This is the first study that investigates LDL subfractions in pregnancy using a method that strictly separates LDL subfractions by virtue of density. The accumulation of buoyant, triglyceride-rich lipoproteins may be related to the down-regulation of maternal lipase activities by placental hormones. As a consequence, the metabolic changes of late pregnancy may result in an increased flux of lipoprotein-derived lipids to the placenta, which, with advancing gestation, increasingly expresses receptors with a high affinity for triglyceride-rich lipoproteins.

Adult↗

PubMed2000

An olive oil-rich diet results in higher concentrations of LDL cholesterol and a higher number of LDL subfraction particles than rapeseed oil and sunflower oil diets.

We investigated the effect of olive oil, rapeseed oil, and sunflower oil on blood lipids and lipoproteins including number and lipid composition of lipoprotein subclasses. Eighteen young, healthy men participated in a double-blinded randomized cross-over study (3-week intervention period) with 50 g of oil per 10 MJ incorporated into a constant diet. Plasma cholesterol, triacylglycerol, apolipoprotein B, and very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) cholesterol concentrations were 10;-20% higher after consumption of the olive oil diet compared with the rapeseed oil and sunflower oil diets [analysis of variance (ANOVA), P < 0.05]. The size of IDL, VLDL, and LDL subfractions did not differ between the diets, whereas a significantly higher number (apolipoprotein B concentration) and lipid content of the larger and medium-sized LDL subfractions were observed after the olive oil diet compared with the rapeseed oil and sunflower oil diets (ANOVA, P < 0.05). Total HDL cholesterol concentration did not differ significantly, but HDL(2a) cholesterol was higher after olive oil and rapeseed oil compared with sunflower oil (ANOVA, P < 0.05).In conclusion, rapeseed oil and sunflower oil had more favorable effects on blood lipids and plasma apolipoproteins as well as on the number and lipid content of LDL subfractions compared with olive oil. Some of the differences may be attributed to differences in the squalene and phytosterol contents of the oils.

Adult↗

PubMed1999

Influence of mild to moderately elevated triglycerides on low density lipoprotein subfraction concentration and composition in healthy men with low high density lipoprotein cholesterol levels.

Epidemiologic studies have shown that a dyslipoproteinemia with low concentrations of high density lipoprotein (HDL) cholesterol and elevated serum triglycerides (TG) is associated with a particularly high incidence of coronary artery disease. This lipid profile is associated with increased concentrations of small, dense low density lipoprotein (LDL) particles. To evaluate the role of mild to moderately elevated TG on the LDL subfraction profile in patients with low HDL cholesterol, concentration and composition of six LDL subfractions was determined by density gradient ultracentrifugation in 41 healthy men (31+/-9 years, body mass index (BMI) 25.1+/-3.9 kg/m2) with equally low HDL cholesterol levels < 0.91 mmol/l but different TG levels: TG < 1.13 mmol/l, n = 16; TG = 1.13-2.26 mmol/l, n = 13: TG = 2.26-3.39 mmol/l, n = 12. Those men with moderately elevated TG levels between 2.26 and 3.39 mmol/l had significantly higher concentrations of very low density lipoprotein (VLDL), intermediate low density lipoprotein (IDL), and small, dense LDL apoB and cholesterol than men with TG < 1.13 mmol/l. With increasing serum TG, the TG content per particle also increased in VLDL, IDL as well as total LDL particles while the cholesterol and phospholipid (PL) content decreased in VLDL and IDL, but not in LDL particles. LDL subfraction analysis revealed that only large, more buoyant LDL particles (d < 1.044 g/ml) but not the smaller, more dense LDL, were enriched in TG. Small, dense LDL particles were depleted of free cholesterol (FC) and PL. This study has shown that in men with low HDL cholesterol levels mild to moderately elevated serum TG strongly suggest the presence of other metabolic cardiovascular risk factors and in particular of a more atherogenic LDL subfraction profile of increased concentration of small, dense LDL particles that are depleted in surface lipids.

Adult↗

PubMed1999

Influence of 4 weeks' intervention by exercise and diet on low-density lipoprotein subfractions in obese men with type 2 diabetes.

Insulin resistance is associated with dyslipoproteinemia characterized by increased serum triglycerides, reduced high-density lipoprotein 2 (HDL2) cholesterol, and increased small, dense low-density lipoprotein (LDL) subfraction particles. Physical activity and weight reduction are known to improve insulin resistance and dyslipoproteinemia, but their influence on LDL subfractions in diabetic patients is unknown. Therefore, we investigated the effect of a 4-week intervention program of exercise (2,200 kcal/wk) and diet (1,000 kcal/d: 50% carbohydrate, 25% protein, and 25% fat; polyunsaturated/saturated fat ratio, 1.0) on glycemic control and HDL and LDL subfractions in 34 obese patients with non-insulin-dependent diabetes (age, 49 +/- 9 years; body mass index [BMI], 33.1 +/- 5.1 kg/m2). Reductions in body weight (P < .001) and improvements in fasting blood glucose, insulin, fructosamine (P < .001), and free fatty acids (P < .01) by intervention were associated with reductions in serum cholesterol and apolipoprotein B (apo B) concentrations in very-low-density lipoprotein (VLDL) (P < .01), intermediate-density lipoprotein (IDL), and small, dense (>1.040 g/mL) LDL particles (P < .001). These data underlie the positive influence of weight reduction induced by exercise and diet on insulin resistance and lipoprotein metabolism in obese diabetic patients, particularly showing improvements of the LDL subfraction profile with a decrease of small, dense LDL particles. This is of particular importance, as these particles have been shown to be associated with coronary artery disease.

Adult↗

PubMed1999

Association of physical fitness with LDL and HDL subfractions in young healthy men.

A dyslipoproteinemia of increased concentrations of small, dense LDL particles and reduced HDL2 cholesterol has shown to be associated with coronary heart disease (CHD). In contrast, an increase in physical fitness and a reduction of body mass index (BMI) improve the lipoprotein profile and reduce the incidence of cardiovascular events. The association of physical exercise, physical fitness, and body weight with an atherogenic lipoprotein subfraction profile has been investigated before in obese subjects, but the relationship is unknown in a healthy non-obese population without insulin resistance or CHD. Therefore, a detailed lipoprotein subfraction profile of 3 HDL and 6 LDL subfractions was determined in 125 healthy men (26+/-5 years). Physical fitness (maximal oxygen consumption, VO2max) was assessed by ergometry and physical activity by questionnaire. Those men with the lowest physical fitness (VO2max < 40 ml/kg/min) and the lowest physical activity score had a significantly less favourable lipoprotein subfraction profile of increased concentration of small, dense LDL particles (d: > 1.044 g/ml) and reduced HDL2a cholesterol than those with a VO2max >50 ml/kg/min. Multivariate regression analysis revealed that concentrations of small, dense LDL particles were primarily determined by BMI whereas HDL2a cholesterol and apolipoprotein A-I were primarily determined by physical fitness. These findings underline the relationship between a good physical fitness, a low body weight, and a favourable lipoprotein subfraction profile even in a healthy young male population.

Adult↗

PubMed1998

[LDL subfractions and coronary heart disease--an overview].

Low density lipoproteins are heterogeneous in particle size, density, and physical as well as chemical properties. Regarding size and density, LDL can be divided into two main profiles, LDL pattern A with elevated concentration of large, buoyant LDL particles and LDL pattern B with increased concentration of small, dense LDL particles. The latter is particularly expressed in insulin resistance and is associated with elevated serum triglycerides and reduced concentrations of HDL and particularly HDL2 cholesterol. The LDL profile of increased concentration of small, dense LDL particles has shown to be associated with an increased risk of cardiovascular events. The LDL profile is partly genetically determined, but can be improved by non-pharmacological (exercise, diet) and pharmacological intervention. It remains to be confirmed whether the LDL subfraction profile is an independent lipid risk factor besides HDL2 cholesterol and triglycerides, but it is certainly a valuable indicator assessing metabolic cardiovascular risk.

Cholesterol, HDL↗

PubMed1998

VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100.

Mutations in the apolipoprotein (apo) B, E (LDL) receptor gene and in the apolipoprotein B-100 gene are the cause of familial hypercholesterolemia (FH) and of familial defective apo B-100 (FDB), respectively. Whether these abnormalities lead to altered production or uptake of very low density lipoprotein (VLDL) or intermediate density lipoprotein (IDL) has not been established previously. Therefore VLDL and IDL apo B-100 kinetics were measured in seven subjects with FH, in six subjects with FDB, and in five normocholesterolemic controls using primed-constant infusions of [1-13C]leucine. Absolute production rates (APR) of VLDL apoB were higher in FH than in controls (27.1+/-1.9 vs. 17.9+/-2.1 mg/kg/day P < 0.03). VLDL APR in FDB were between those of FH and controls (24.3+/-4.8 mg/kg/day), and demonstrated a relatively large inter-individual variability. The increase in VLDL APR in FH resulted in higher fasting serum triglyceride concentrations than in controls (P < 0.05), whereas in FDB triglycerides were between those observed in FH and in controls. A significant correlation was observed between VLDL apoB APR and serum triglycerides in FH and in FDB; the correlation coefficient for all subjects was r = 0.84 (P < 0.0001), indicating that the major determinant of serum triglyceride concentrations was VLDL apoB APR. IDL apoB APR was lower in FH and in FDB compared to controls (P < 0.03 P < 0.02, respectively): and its fractional catabolic rate (FCR) was slightly lower in FH and in FDB, resulting in similar plasma IDL apoB concentrations in all three groups of subjects. IDL apoB APR in FH were negatively correlated with LDL cholesterol concentrations (r = -0.89; P < 0.001); LDL cholesterol concentrations correlated positively with the part of VLDL that did not appear in IDL (r = 0.82 P < 0.02), by-passing therefore the delipidation cascade. In conclusion the data demonstrate increased VLDL apoB production rates in FH. VLDL and IDL kinetics differ when LDL concentrations are elevated either due to a LDL receptor defect or due to defective apolipoprotein B-100.

Adult↗

PubMed1997

Relationship of serum ferritin concentrations with metabolic cardiovascular risk factors in men without evidence for coronary artery disease.

Elevated serum ferritin concentrations between 200 and 500 microg/l have been found to be a strong risk factor for acute myocardial infarction in Finnish men, but the reason for this association is still uncertain. In the Finnish population ferritin concentrations correlated with factors of insulin resistance syndrome. As these factors have been found to be associated with an LDL subfraction phenotype of increased concentrations of small, dense LDL particles, we hypothesized an association between ferritin and an atherogenic LDL subfraction profile, a finding which could be an explanation for the observed relationship between ferritin and atherosclerosis. Therefore we determined serum ferritin levels, metabolic cardiovascular risk factors, and the LDL subfraction phenotype in 93 healthy men without signs for infection or coronary heart disease. We found that men with moderately elevated ferritin levels (200-500 microg/l; n = 31) had a significantly worse coronary risk profile than men with lower levels ( < 200 microg/l; n = 62). Elevated ferritin concentrations were associated with significantly higher values for serum triglycerides, VLDL cholesterol, VLDL apolipoprotein B (P < 0.01), IDL cholesterol, fasting glucose (P < 0.05) and uric acid (P < 0.01), and lower levels for HDL2b and HDL2a cholesterol and apolipoprotein A-I (P < 0.05), and lipoprotein(a) (P < 0.01). Elevated ferritin levels were, however, not associated with an unfavourable LDL subfraction profile of increased concentrations of small, dense LDL particles.

Adult↗

PubMed1997

Differences in the concentration and composition of low-density lipoprotein subfraction particles between sedentary and trained hypercholesterolemic men.

There is evidence that a low-density lipoprotein (LDL) subfraction profile of increased concentrations of small, dense LDL particles is less common among trained than among sedentary normocholesterolemic men, but it is still uncertain whether there is a similar association in hypercholesterolemia also. Therefore, we determined the lipid and apolipoprotein concentration and composition of six LDL subfractions (density gradient ultracentrifugation) in 20 physically fit, regularly exercising (>three times per week) hypercholesterolemic men and 20 sedentary hypercholesterolemic controls. Trained (maximal oxygen consumption [VO2max], 57.3 +/- 7.4 mL/kg/min) and sedentary (VO2max, 37.5 +/- 8.8 mL/kg/min) individuals (aged 35 +/- 11 years; body mass index [BMI], 23.9 +/- 2.7 kg/m2) were matched for LDL apolipoprotein (apo) B levels (108 +/- 23 and 112 +/- 36 mg/dL, respectively). Trained subjects had significantly lower serum triglyceride (P < .05) and very-low-density lipoprotein (VLDL) cholesterol levels (P < .05) and higher high-density lipoprotein 2 (HDL2) cholesterol levels (P < .01) than sedentary controls. LDL particle distribution showed that trained individuals had significantly less small, dense LDL (d = 1.040 to 1.063 g/mL) and more large LDL (d = 1.019 to 1.037 g/mL) subfraction particles than sedentary controls, despite equal total LDL particle number. Analysis of LDL composition showed that LDL particles of hypercholesterolemic trained men had a higher free cholesterol content than LDL of untrained hypercholesterolemic men. Small, dense LDL in hypercholesterolemic trained men were richer in phospholipids than those in sedentary controls. These data demonstrate the significant influence of aerobic fitness on lipoprotein subfraction concentration and composition, thereby emphasizing the role of exercise in the treatment and risk reduction of hypercholesterolemia.

Centrifugation, Density Gradient↗

PubMed1997

Structural and compositional modifications of diabetic low-density lipoproteins influence their receptor-mediated uptake by hepatocytes.

Dyslipoproteinaemia is an important risk factor for the development of atherosclerosis in noninsulin-dependent diabetes mellitus (NIDDM). This study shows that the uptake of low-density lipoproteins (LDLs) prepared from the plasma of patients with NIDDM in cultured human hepatoma cells is largely reduced. In addition, diabetic LDL was less effective in suppressing intracellular cholesterol synthesis. This is because of physicochemical and biochemical differences between lipoproteins from diabetic and from normal individuals. LDL from patients with NIDDM was abnormal with regard to charge, the degree of glycation, the lipid composition and the conformation of the apolipoprotein B receptor-binding domain. The diminished receptor-mediated uptake of apolipoprotein B-containing lipoproteins in diabetic individuals most probably leads to the accumulation of these lipoproteins in vivo and may be of great importance to the pathogenesis of atheroclerosis in these patients.

Acetic Acid↗

PubMed1997

Uptake and metabolism of lipoproteins from patients with diabetes mellitus type II by glomerular epithelial cells.

BACKGROUND: Recent studies suggest that dyslipidaemia accelerates the progression of diabetic nephropathy, but the various pathomechanisms underlying such abnormalities are not completely delineated. METHODS: We isolated, radiolabelled, and characterized very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) from eight diabetic patients with moderate impairment of renal function and dyslipidaemia and studied their interaction with LDL receptors in human glomerular epithelial cells. RESULTS: While diabetic VLDL showed no compositional changes, LDL particles contained a higher proportion of triglycerides at the expense of cholesterol in comparison with healthy controls. Despite differences in composition, both VLDL and LDL from patients exhibited reduced receptor affinity and cellular uptake capacity by glomerular epithelial cells. Since LDL composition was altered intracellular cholesterol homeostasis was investigated. Due to reduced cholesterol content and lower uptake capacity, diabetic LDL were less effective in suppressing intracellular sterol synthesis and in activating acylcholesterol acyltransferase than LDL from controls. Electrophoretic mobility of apoB from diabetic patients was enhanced as compared to controls, most probably due to the higher degree of glycation (17 + 1.7 versus 11 + 1%, P < 0.05) but not to oxidation (TBARS 0.5 + 0.2 versus 0.2 + 0.1 mumol/1). Oxidized LDL was not taken up in significant amounts, indicating no scavenger receptor activity in glomerular epithelial cells. CONCLUSION: The receptor-specific uptake of diabetic VLDL and LDL by glomerular epithelial cells is impaired. Compositional changes of the LDL particle and glycation of the protein moiety may contribute to altered glomerular uptake. However, glycation of the protein moiety may be superior to compositional changes. Because glomerular structures like mesangial matrix and endothelial cells are known for preferential binding of modified lipoproteins, further studies are required to elucidate their potential role in the progression of diabetic glomerulosclerosis.

Aged↗