Plasma proprotein convertase subtilisin–kexin type 9 is predominantly related to intermediate density lipoproteins

ObjectivesProprotein convertase subtilisin–kexin type 9 (PCSK9) is a key regulator of low density lipoprotein (LDL) receptor processing, but the PCSK9 pathway may also be implicated in the metabolism of triglyceride-rich lipoproteins. Here we determined the relationship of plasma PCSK9 with very low density lipoprotein (VLDL) and LDL subfractions.Design and methodsThe relationship of plasma PCSK9 (sandwich enzyme-linked immunosorbent assay) with 3 very low density lipoprotein (VLDL) and 3 low density lipoprotein (LDL) subfractions (nuclear magnetic resonance spectroscopy) was determined in 52 subjects (30 women).ResultsIn age- and sex-adjusted analysis plasma PCSK9 was correlated positively with total cholesterol, non-high density lipoprotein cholesterol and LDL cholesterol (r = 0.516 to 0.547, all p < 0.001), as well as with triglycerides (r = 0.286, p = 0.044). PCSK9 was correlated with the VLDL particle concentration (r = 0.336, p = 0.017) and with the LDL particle concentration (r = 0.362, p = 0.010), but only the relationship with the LDL particle concentration remained significant in multivariable linear regression analysis. In an analysis which included the 3 LDL subfractions, PCSK9 was independently related to intermediate density lipoproteins (IDL) (p < 0.001), but not to other LDL subfractions.ConclusionsThis study suggests that plasma PCSK9 predominantly relates to IDL, a triglyceride-rich LDL subfraction. The PCSK9 pathway may affect plasma triglycerides via effects on the metabolism of triglyceride-rich LDL particles.     

HDL 2 Particles are associated with hyperglycaemia,lower PON1 activity and oxidative stress in type 2 diabetes mellitus patients

ObjectivesIn this study we examined the relationship of oxidative stress and hyperglycaemia to antioxidative capacity of high-density cholesterol (HDL-C) particles in type 2 diabetes mellitus (DM).Design and methodsOxidative stress status parameters (superoxide anion (O₂^?), superoxide dismutase (SOD) activity and paraoxonase (PON1) status were assessed in 114 patients with type 2 DM and 91 healthy subjects. HDL particle diameters were determined by non-denaturing polyacrylamide gradient (3–31%) gel electrophoresis.ResultsPatients had significantly higher concentrations of oxidative stress parameter O₂^?(p < 0.001) and antioxidative defence, SOD activity (p < 0.001). Paraoxonase activity was significantly lower in diabetics (p < 0.001). The PON1₁₉₂ phenotype distribution among study groups was not significantly different. HDL 3 phenotype was significantly prevalent among patients (p < 0.001). Paraoxonase activity was significantly lower in patients with predominantly HDL 2 particles than in controls.ConclusionsThe results of our current study indicate that the diabetic HDL 2 phenotype is associated with hyperglycaemia, lower PON1 activity and elevated oxidative stress.     

Association of Apo(a)isoform size with dyslipoproteinemia in male Venous Thrombosis patients

BackgroundLp(a) is a proatherogenic lipoprotein that may also be prothrombotic. Apo(a) size isoforms have differential effects on fibrinolysis. Whereas Lp(a) concentrations have been linked to venous thromboembolic disease (VTE) risk, apo(a) polymorphisms in VTE have not been studied.MethodsWe used a standardized high resolution agarose gel electrophoresis technique to determine apo(a) isoform size, and a Lp(a) immunoassay insensitive to apo(a) size to measure Lp(a) concentration in 46 men with VTE and 46 age-matched healthy controls.ResultsApo(a) isoform distribution in VTE cases and controls was bimodal and VTE patients tended to have more medium-sized isoforms K₄-(19-27) (54.3% vs. 34.8%, p = 0.06). Cases and controls had the same median predominant apo(a) size isoform (23.5 K₄ repeats) and comparable Lp(a) concentrations. However, subgroup analysis based on apo(a) isoform size (K₄ ≤ 23 or K₄ ≥ 24) revealed that cases in the K₄ ≥ 24 subgroup had higher Lp(a) concentrations than the controls in this isofrom subgroup (14.5 mmol vs. 6.6 mmol, p = 0.029). Also, dyslipoproteinemia (smaller LDL and HDL particles, higher LDL and lower HDL parameters) was strongly associated with VTE only in this larger apo(a) isoform group.ConclusionsThese observations provide the first evidence that determination of apo(a) isoforms may provide useful novel insights into VTE risk.     

Comparative proteomic profiling of plasma very-low-density and low-density lipoproteins

BackgroundLow-density lipoprotein (LDL) is a natural metabolite of very-low-density lipoprotein (VLDL) in the circulation. Systematic investigation of total protein components and dynamics might provide insights into this normal metabolic process.MethodsVLDL and LDL were purified from normolipidemia pooled plasma by gradient ultracentrifugation with either ionic or non-ionic media. The protein contents were compared by liquid chromatography tandem mass analyses based on isobaric tag for relative and absolute quantitation and two-dimensional gel electrophoresis.ResultsOur comparative lipoproteomes revealed 21 associated proteins. Combined with Western blot analysis, and on the basis of the differential expression levels we classified them into 3 groups: (i) VLDL > LDL [apolipoprotein (apo) A-IV, apo(a), apoCs, apoE, apoJ and serum amyloid A-4]; (ii) VLDL < LDL [albumin, α-1-antitrypsin, apoD, apoF, apoM, and paraoxonase-1]; and (iii) VLDL = LDL [apoA-I, apoA-II, apoB-100, apoL-I and prenylcysteine oxidase-1]. The apoA-I level positively correlated with PCYOX1 but negatively with apoM in VLDL and LDL. Furthermore, the two-dimensional maps displayed 5 apoA-I isoforms in which phosphorylation at Ser55, Ser166, Thr185, Thr221 and Ser252 residues were identified.ConclusionsThis study revealed the VLDL- and LDL lipoproteomes and the full-spectrum protein changes during physiological VLDL-to-LDL transition. It provides a valuable dataset VLDL and LDL proteomes potentially applied to the development of diagnostics.     

Comparative study between anion-exchange HPLC and homogeneous assay methods in regard to the accuracy of high- and low-density lipoprotein cholesterol measurement

Objectives:A convenient method based on anion-exchange HPLC was recently developed to determine cholesterol levels of lipoproteins (HDL, LDL, IDL, VLDL, and chylomicron). The present study was performed to compare this HPLC method to homogenous assay in regard to measurement accuracy of HDL and LDL cholesterol.Design and methods:Serum samples (n = 105), including three samples from cholestasis patients, were measured by homogenous assay with Cholestest-LDL and CholestestN-HDL (Daiichi Chemicals, Tokyo) and by HPLC as reported previously (J Lipid Res 2003; 44: 1404–12).Results:The homogenous assay for HDL cholesterol correlated strongly with the HPLC method for HDL cholesterol (r = 0.976). Two samples from cholestasis patients could not be measured by homogenous assay but were measured by HPLC. The homogenous assay for LDL cholesterol correlated modestly with the HPLC method for LDL cholesterol (r = 0.823). Three outlier samples, from cholestasis patients with serum cholesterol levels > 17 mmol/L, were observed in this correlation analysis. Homogenous assay data showed that these LDL cholesterol levels were 15.2–34.7 mmol/L. However, HPLC data showed that these LDL cholesterol levels were 3.6–8.2 mmol/L, and that the major lipoprotein fractions were VLDL and IDL. The difference in LDL cholesterol levels (homogenous assay data minus HPLC data) was positively correlated with VLDL cholesterol levels.Conclusions:When measuring samples from cholestasis patients, homogenous assay may give inaccurate results. In contrast, the HPLC method is likely to be capable of accurately measuring HDL and LDL cholesterol levels without the involving VLDL.     

Mutations in APOA-I and ABCA1 in Norwegians with low levels of HDL cholesterol

BackgroundEpidemiological studies have shown that low levels of plasma high density lipoprotein (HDL) cholesterol are associated with increased risk of ischemic heart disease (IHD), but it appears that genetic forms of low HDL cholesterol levels, as opposed to lifestyle-induced low levels of HDL cholesterol, do not result in increased risk of IHD. Therefore, the etiology of reduced levels of plasma HDL cholesterol may represent a factor that should be considered in risk stratification with respect to primary prevention. Genes encoding proteins involved in HDL metabolism, such as the ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein (apo) A-I genes, are candidate genes for harboring mutations that lead to low HDL cholesterol levels.MethodsThe ABCA1 and apoA-I genes in 56 Norwegian patients, with a mean HDL cholesterol level of 0.53 (± 0.15) mmol/l, were subjected to DNA sequencing.ResultsSeveral mutations were identified in the ABCA1 gene, and two mutations were identified in the apoA-I gene. A total of 18 patients (32%) were carriers of mutations considered to be pathogenic. Their mean HDL cholesterol level was 0.45 (± 0.15) mmol/l compared to 0.57 (± 0.14) mmol/l in noncarriers (p < 0.005).ConclusionMutations in the genes encoding ABCA1 and apoA-I are common in Norwegians, with a markedly decreased HDL cholesterol level.     

High density lipoprotein-anionic peptide factor effect on reverse cholesterol transport in type 2 diabetic patients with and without coronary artery disease

ObjectivesTo verify if HDL3 Anionic Peptide Factor (HDL3-APF) is as an apolipoprotein that promotes the reverse cholesterol transport.Design and methodsWe investigated a possible association between plasma HDL3-APF concentration, cholesterol efflux from Fu5AH cells and cholesteryl ester transfer protein (CETP) activity in type 2 diabetic patients with coronary artery disease (CAD) (n = 36), those without CAD (n = 20), and 37 healthy subjects.ResultsPlasma APF concentrations were decreased in diabetics with CAD compared to controls (p < 0.01). Cellular cholesterol efflux was decreased in diabetics without and with CAD, (p < 0.01 and p < 0.001 respectively). CETP activity was significantly elevated in all patient groups. Multiple linear regression analysis shows that cholesterol efflux was independently and positively related only to APF concentrations in controls.ConclusionsAPF is likely to be a key independent factor for promoting cellular cholesterol efflux in healthy subjects. However this association is altered in type 2 diabetes.     

Profiles of inflammatory markers and lipoprotein subclasses in patients undergoing continuous ambulatory peritoneal dialysis

BackgroundPatients undergoing continuous ambulatory peritoneal dialysis (CAPD) often have inflammation and dyslipidemia that accelerate to atherosclerosis. This study aimed to evaluate chronic inflammation and dyslipidemia in CAPD patients.MethodsWe measured inflammatory markers and lipoprotein subclasses in 20 CAPD patients (12 men and 8 women, aged 59.5 ± 9.9 y) and 20 gender-matched controls. Lipoproteins were separated by high-performance liquid chromatography (HPLC) using an anion-exchange column.ResultsHigh-sensitivity C-reactive protein and serum amyloid A protein (SAA) were higher among CAPD patients vs. controls (1.6 ± 2.2 vs. 0.8 ± 1.2 mg/l, p < 0.05; 11.9 ± 12.8 vs. 4.5 ± 2.4 mg/l). HPLC analysis revealed that chylomicron, VLDL, and IDL cholesterol levels were higher among CAPD vs. controls. In contrast, HDL cholesterol was lower among CAPD patients vs. controls. In the subgroup analysis, SAA levels were significantly lower among patients receiving CAPD for > 3 y than among controls. However, IDL cholesterol was consistently higher among CAPD patients vs. controls.ConclusionsCAPD patients have chronic inflammation and dyslipidemia. IDL cholesterol is the only lipoprotein subclass that is consistently elevated regardless of CAPD duration. More attention should be paid to dyslipidemia in the management of the CAPD patients.     

Carotid intima media thickness is related positively to plasma pre ß-high density lipoproteins in non-diabetic subjects

BackgroundLipid-poor or lipid-free high density lipoprotein (HDL) particles, designated pre ß-HDL, stimulate removal of cell-derived cholesterol to the extracellular compartment, which is an initial step in the reverse cholesterol transport pathway. Pre ß-HDL levels may be elevated in subjects with established cardiovascular disease. We determined the relationship of carotid intima media thickness (IMT), a marker of subclinical atherosclerosis, with pre ß-HDL in subjects without clinically manifest cardiovascular disease.MethodsIMT and plasma pre ß-HDL, assayed by crossed immuno-electrophoresis, were determined in 70 non-diabetic subjects (aged 56 ± 9 years; non-smokers only; 27 women).ResultsIMT was correlated positively with pre ß-HDL, both expressed as plasma apolipoprotein (apo) A-I concentration (r = 0.271, p = 0.023) and as% of apo A-I (r = 0.341, p = 0.004). In contrast, IMT was correlated inversely with HDL cholesterol (r = ? 0.253, p = 0.035). IMT was also related positively to pre ß-HDL after adjustment for age, sex, systolic blood pressure (in apoA-I concentration, ß = 0.203, p = 0.043; in% of plasma apoA-I, ß = 0.235, p = 0.023). IMT remained associated with pre ß-HDL after additional adjustment for either body mass index, plasma glucose, cholesterol, triglycerides, HDL cholesterol, apoA-I and apoB.ConclusionSubclinical atherosclerosis may relate to higher plasma pre ß-HDL independently of apoA-I and HDL cholesterol levels.     

Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus

ObjectivesTo find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran.Design and methodsThe MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric T2DM patients by PCR-RFLP.ResultsThe possession of both MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold (p = 0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is sufficient to increase the risk of macroalbuminuria in T2DM patients by 4.1 and 5.5 times (p = 0.027, and p = 0.006, respectively). The concomitant presence of both 677T and 1298C alleles act in synergy to increase the risk of macroalbuminuria by 20.4-fold (p < 0.001) and progression of DN from microalbuminuria to macroalbuminuria (OR = 4.73, p = 0.01).ConclusionBoth MTHFR 677T and 1298C alleles increased the susceptibility to the onset and progression of DN in Iranians with T2DM.     

Serum paraoxonase-1 activity is more closely related to HDL particle concentration and large HDL particles than to HDL cholesterol in Type 2 diabetic and non-diabetic subjects

Objectives

We determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2 diabetes mellitus (T2DM).

Design and methods

Serum PON-1 (arylesterase activity) and HDL subfractions (nuclear magnetic resonance spectroscopy) were determined in 67 T2DM patients and in 56 non-diabetic subjects.

Results

PON-1 activity, HDL cholesterol and apoA-I were decreased in T2DM (all p < 0.05). The HDL particle concentration was unaltered, but large HDL particles, medium HDL particles and HDL particle size were decreased, whereas small HDL particles were increased in T2DM (all p < 0.05). PON-1 was more closely related to HDL cholesterol than to apoA-I (p = 0.001). In turn, the positive relationship of PON-1 with the HDL particle concentration and with large HDL particles was stronger than that with HDL cholesterol (both p < 0.01). The inverse relationship of PON-1 with T2DM was only modestly attenuated by HDL cholesterol or HDL particle characteristics.

Conclusions

PON-1 activity is more closely related to the HDL particle concentration or large HDL particles than to HDL cholesterol. Impaired PON-1 activity in T2DM is not to a considerable extent explained by altered HDL subfraction levels.     

Relationship of proprotein convertase subtilisin-kexin type 9 levels with resistin in lean and obese subjects

ObjectivesProprotein convertase subtilisin-kexin type 9 (PCSK9), a key regulator of low density lipoprotein receptor expression, has recently been reported to be upregulated by resistin in HepG2 cells and human primary hepatocytes. Whether this translates into a positive relationship of plasma PCSK9 with resistin levels in humans with varying degrees of obesity is unknown.Design and methodsWe assessed the extent to which plasma PCSK9 levels are determined by resistin in individuals with varying degrees of obesity.ResultsIn 80 subjects (35 women; no diabetes mellitus) with body mass index ranging from 19.4 to 40.4 kg/m², plasma PCSK9 levels were not positively related to resistin (r = ? 0.161, p = 0.154). Despite positive correlations of non-high density lipoprotein cholesterol (r = 0.378, p < 0.001), low density lipoprotein (r = 0.292, p < 0.01) and apolipoprotein B (apoB) (r = 0.266, p < 0.05) with PCSK9, none of these apolipoprotein (apo) B-containing lipoprotein measures was positively related to resistin (p > 0.10 for all). In subjects with BMI < 25.0 kg/m² (n = 38), PCSK9 was even inversely related to resistin (r = ? 0.322, p = 0.049), and this relationship remained present after controlling for either leptin (p = 0.027) or insulin resistance (P = 0.031). In subjects with BMI ≥ 25.0 kg/m² (n = 42), PCSK9 was unrelated to resistin (r = ? 0.064, p = 0.69).ConclusionsThis study demonstrates that there is no positive association of plasma PCSK9 with resistin in lean and moderately obese individuals. Our data question whether circulating resistin is a physiologically important determinant of higher PCSK9 levels.     

Influence of SCARB1 polymorphisms on serum lipids of hypercholesterolemic individuals treated with atorvastatin

BackgroundThe SR-BI is a key component on the cholesterol metabolism. Polymorphisms in the SR-BI gene (SCARB1) were related with variations on plasma lipoprotein profile and other risk factors for cardiovascular disease. We tested the relationship of 3 SCARB1 single nucleotide polymorphisms (SNPs) with hypercholesterolemia in a Brazilian population and whether these variants can influence lipid-lowering response to atorvastatin.Methodsc.4G>A, c.726+54C>T and c.1050C>T SNPs and serum concentrations of lipid and apolipoproteins were evaluated in 147 hypercholesterolemic (HC) and 185 normolipidemic (NL) unrelated Brazilian subjects. HC patients were treated with atorvastatin (10 mg/day/4 weeks).ResultsFrequencies of SCARB1 polymorphisms were similar between the HC and NL groups (p > 0.05). The T allele for c.726+54C>T was associated with higher LDL-c in NL and with higher apoB and apoB/apoAI in HC (p < 0.05). HC individuals carrying c.1050C allele carriers (CC and CT genotypes) had lower change of total cholesterol, LDL-c, apoB and apoB/apoAI ratio (p < 0.05) than the TT genotype carriers in response to atorvastatin.ConclusionThe SCARB1 polymorphisms are related with variations in serum lipids in the Brazilian population and c.1050C>T SNP is associated with lipid-lowering atorvastatin response.     

Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: Case–control cross-sectional study

ObjectiveVascular endothelial growth factor A (VEGF) and its receptor KDR play central roles in angiogenesis and vascular repair, which occur in diabetic vascular complications, such as MI. The aim of our study was to investigate if polymorphisms rs2071559 and rs2305948 in the kinase insert domain-containing receptor (KDR) gene are associated with myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM).Design and methodsThe association of KDR − 604T>C (rs2071559) and 1192G>A (rs2305948) polymorphisms was tested in a case–control cross-sectional study including 171 subjects with T2DM and MI compared to 855 subjects with T2DM without coronary artery disease (CAD). In addition, VEGF serum levels were analyzed in 98 subjects with type 2 diabetes without CAD.ResultsA significantly higher frequency of the CC genotype of the KDR − 604T>C (rs2071559) polymorphism was found in diabetic patients with MI compared to diabetic patients without CAD (27.5% vs. 21.1%, p = 0.04). On the other hand, the 1192G>A (rs2305948) polymorphism was not associated with MI in subjects with type 2 diabetes. Significantly higher VEGF serum levels were found in subjects with the − 604CC genotype compared to those with other (CT + TT) genotypes (73.8 ± 22.1 ng/l vs. 58.1 ± 18.5 ng/l; p < 0.01). Multiple logistic regression analysis adjusted for age, arterial hypertension, LDL cholesterol, HDL cholesterol and hsCRP revealed that carriers of the − 604CC genotype (rs2071559) had a 1.6-fold higher risk for MI (OR = 1.6; 95% CI = 1.1–2.1; p = 0.022).ConclusionThe present study demonstrates that the CC genotype of the KDR − 604T>C polymorphism (rs2071559) is a possible risk factor for MI in Caucasians with T2DM.     

Roles of high apolipoprotein E blood levels and HDL in development of familial dysbetalipoproteinemia in ε2ε2 subjects

ObjectiveFamilial dysbetalipoproteinemia (FD) or Type III hyperlipoproteinemia is a mixed hyperlipidemia closely associated with the ε2ε2 genotype of the common APOE polymorphism although not all homozygotes progress to FD. Unlike the polymorphism, few studies explore effects of apolipoprotein E (apoE) blood levels on FD development. Likewise, despite the known apoE2 lipoprotein binding preference for high-density lipoprotein (HDL); little work exists exploring HDL in FD. Accordingly, this study was undertaken to investigate potential roles in FD development for apoE and HDL. Additionally, insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were investigated in view of reports linking insulin resistance to FD.MethodsAPOE genotyping and levels of apoE, apolipoprotein A-I (apoA-I), apolipoprotein A-II (apoA-II), insulin, HOMA-IR, lipids, and NMR lipoprotein analysis were determined in a cohort of healthy individuals (N = 7169). A lipid-based algorithm identified FD in 24 of 52 e2e2 subjects. Logistic regression modeling assessed associations of FD development with measured variables.ResultsUnivariate models revealed associations with FD significant and positive for apoE, apoA-II/apoA-I, apoA-I/HDL-C, apoA-II/HDL-C, and HOMA-IR. For HDL-C, association was significant but inverse. Results of multivariable models containing apoE with single parameters added revealed statistical significance only for the apoA-II/HDL-C ratio (OR 10.52, 95%CI 1.17–94.79, p = 0.036) concurrent with significance for apoE (OR 2.21, 95%CI 1.06–4.65, p = 0.035). Interaction was not demonstrated (p = 0.36). NMR results revealed for FD versus nonFD subjects generally higher levels of VLDL and small HDL and for IDL few differences.ConclusionHigh apoE and high apoA-II/HDL-C independently associate with FD development in ε2ε2 individuals.     

Effects of isotretinoin on serum lipids and lipoproteins,liver and thyroid function

Seven patients with severe rosacea were treated with 1 mg/kg per day isotretinoin for 12 wk. There were significant increases in serum triglyceride (p < 0.001) and cholesterol (p < 0.001). Triglyceride associated with very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) increased (p < 0.01), cholesterol in VLDL and LDL increased (p < 0.01), and levels of HDL cholesterol decreased (p < 0.01). There were changes in indices of liver function, with increased levels of γ-glutamyltransferase (GGT) (p < 0.01), alkaline phosphatase (ALP) (p < 0.01) and aspartate aminotransferase (AST) (p < 0.01), and decreased bilirubin levels (p < 0.05). Although levels of thyroxine and triiodothyronine were lower after treatment (p < 0.05), there were no changes in basal levels of thyroid-stimulating hormone (TSH), luteinizing hormone (LH) or follicle-stimulating hormone (FSH), and responses to thyrotrophin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) were unchanged. These changes may partially be explained by induction of hepatic microsomal enzymes by isotretinoin.     

Differential dyslipidemia associated with albuminuria in type 2 diabetic patients in Taiwan

BackgroundThis study evaluated the lipid abnormalities associated with different stages of albuminuria in type 2 diabetic patients.Methods and resultsA total of 549 patients (245 men and 304 women) with mean age of 63.4 were studied. Normoalbuminuria (n = 251), microalbuminuria (n = 242) and macroalbuminuria (n = 56) were defined as albumin-to-creatinine ratio of < 30, 30–299 and ≥ 300 μg/mg, respectively. Lipid parameters included total cholesterol, triglyceride (TG), high- and low-density lipoprotein (LDL) cholesterol, apolipoproteins A1 and B (ApoB), and lipoprotein(a) [Lp(a)]. Results showed that ApoB differed significantly (p < 0.05) between normoalbuminuria and microalbuminuria/macroalbuminuria and Ln[Lp(a)] differed between normoalbuminuria/microalbuminuria and macroalbuminuria. Ln(TG) increased progressively with increasing albuminuria. In multivariate logistic regression analyses, only ApoB showed significant odds ratio (95% confidence interval) for microalbuminuria: 1.013 (1.004–1.022); and both ln(TG) and ln[Lp(a)] were significant for macroalbuminuria [respective odds ratios: 1.995 (1.010–3.938) and 1.708 (1.200–2.430)].ConclusionsA differential dyslipidemia is observed for microalbuminuria and macroalbuminuria. Apo(B) and Lp(a) increase at the stages of microalbuminuria and macroalbuminuria, respectively. However, TG increases significantly throughout the three stages of albuminuria.     

Relation of atrial fibrillation (AF) and change of lipoproteins: Male patients with AF exhibited severe pro-inflammatory and pro-atherogenic properties in lipoproteins

ObjectivesThis study was designed to search putative biomarkers for detection of relatively young-onset atrial fibrillation (AF).Design and methodsWe analyzed serum lipoproteins from male patients with paroxysmal AF (48 ± 9 years old, n = 29) and controls with similar age (50 ± 10 years old, n = 27), who visited our hospital for radiofrequency catheter ablation due to paroxysmal supraventricular tachycardia.ResultsAlthough the AF group showed normal serum cholesterol level, they exhibited 16% lower HDL-cholesterol and 13% higher serum cholesteryl ester transfer protein activity than those of the control group. The AF group showed elevated levels of serum triglyceride (TG) and C-reactive protein with hyperuricemia. However, there was no difference between serum levels of creatinine, troponin I, and serum amyloid A. All lipoproteins from the AF group contained higher level of TG, oxidized species, and advanced glycated end products. LDL from the AF group (AF-LDL) showed 2.7-fold more content of malondialdehyde than the control group (p < 0.04) and exhibited higher sensitivity of oxidation. HDL-associated paraoxonase from the AF group showed impaired antioxidant ability and lowered expressional level of apoA-I (p < 0.01) and paraoxonase (p < 0.005) in HDL₃.ConclusionLipoprotein properties were severely impaired in the AF group with increased extent of oxidation and inflammation. The modified lipoprotein properties with impaired antioxidant functions can be used as a putative biomarker for prognostic detection for the relatively young onset AF.     

Effects of endurance and endurance–strength exercise on biochemical parameters of liver function in women with abdominal obesity

IntroductionObesity is a risk factor of nonalcoholic fatty liver disease. Although the standard therapy for obesity involves physical exercise, well-planned studies of the changes in liver function in response to different exercise intensities in obese subjects are scarce. The aim of the present study was to examine a question of how does exercise mode affect the liver function.Material and methods44 women with abdominal obesity were randomized into two exercise groups: endurance (group A) and endurance-strength (group B). Women in each group exercised for 60 min 3 times/week for a 3-month period. Markers of liver function: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) activities, and bilirubin levels were quantified.ResultsWe found significant differences in ALT (p < 0.01) and AST (p < 0.05) activities between group A and B after training exercise. Blood ALT and AST tended to decrease in group B, increase in group A. Significant reduction in serum GGT level after exercise in both groups was observed (p < 0.001, group A; p < 0.01, group B). Neither endurance nor endurance-strength exercise led to changes in serum ALP activity and total or direct bilirubin level. However, endurance-strength training resulted in significant decreases in serum indirect bilirubin (p < 0.05). Strong positive correlations between serum indirect bilirubin and body mass (r = 0.615; p = 0.0085) and BMI (r = 0.576; p = 0.0154) were found after endurance-strength exercise (group B).ConclusionThe mode of exercise does matter: endurance-strength exercise led to a greater improvement, compared to endurance exercise, in the liver function in women with abdominal obesity.