Blueberries decrease cardiovascular risk factors in obese men and women with metabolic syndrome

Among all fruits, berries have shown substantial cardio-protective benefits due to their high polyphenol content. However, investigation of their efficacy in improving features of metabolic syndrome and related cardiovascular risk factors in obesity is limited. We examined the effects of blueberry supplementation on features of metabolic syndrome, lipid peroxidation, and inflammation in obese men and women. Forty-eight participants with metabolic syndrome [4 males and 44 females; BMI: 37.8 +/- 2.3 kg/m(2); age: 50.0 +/- 3.0 y (mean +/- SE)] consumed freeze-dried blueberry beverage (50 g freeze-dried blueberries, approximately 350 g fresh blueberries) or equivalent amounts of fluids (controls, 960 mL water) daily for 8 wk in a randomized controlled trial. Anthropometric and blood pressure measurements, assessment of dietary intakes, and fasting blood draws were conducted at screening and at wk 4 and 8 of the study. The decreases in systolic and diastolic blood pressures were greater in the blueberry-supplemented group (- 6 and - 4%, respectively) than in controls (- 1.5 and - 1.2%) (P lt 0.05), whereas the serum glucose concentration and lipid profiles were not affected. The decreases in plasma oxidized LDL and serum malondialdehyde and hydroxynonenal concentrations were greater in the blueberry group (- 28 and - 17%, respectively) than in the control group (- 9 and - 9%) (P lt 0.01). Our study shows blueberries may improve selected features of metabolic syndrome and related cardiovascular risk factors at dietary achievable doses.

Berries:emerging impact on cardiovascular health

Berries are a good source of polyphenols, especially anthocyanins, micronutrients, and fiber. In epidemiological and clinical studies, these constituents have been associated with improved cardiovascular risk profiles. Human intervention studies using chokeberries, cranberries, blueberries, and strawberries (either fresh, or as juice, or freeze-dried), or purified anthocyanin extracts have demonstrated significant improvements in LDL oxidation, lipid peroxidation, total plasma antioxidant capacity, dyslipidemia, and glucose metabolism. Benefits were seen in healthy subjects and in those with existing metabolic risk factors. Underlying mechanisms for these beneficial effects are believed to include upregulation of endothelial nitric oxide synthase, decreased activities of carbohydrate digestive enzymes, decreased oxidative stress, and inhibition of inflammatory gene expression and foam cell formation. Though limited, these data support the recommendation of berries as an essential fruit group in a heart-healthy diet.

Freeze-dried strawberry powder improves lipid profile and lipid peroxidation in women with metabolic syndrome:baseline and post intervention effects

Strawberry flavonoids are potent antioxidants and anti-inflammatory agents that have been shown to reduce cardiovascular disease risk factors in prospective cohort studies. Effects of strawberry supplementation on metabolic risk factors have not been studied in obese populations. We tested the hypothesis that freeze-dried strawberry powder (FSP) will lower fasting lipids and biomarkers of oxidative stress and inflammation at four weeks compared to baseline. We also tested the tolerability and safety of FSP in subjects with metabolic syndrome. FSP is a concentrated source of polyphenolic flavonoids, fiber and phytosterols.

Increased methionine sulfoxide content of apoA-I in type 1 diabetes

Cardiovascular disease is a major cause of morbidity and premature mortality in diabetes. HDL plays an important role in limiting vascular damage by removing cholesterol and cholesteryl ester hydroperoxides from oxidized low density lipoprotein and foam cells. Methionine (Met) residues in apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, reduce peroxides in HDL lipids, forming methionine sulfoxide [Met(O)]. We examined the extent and sites of Met(O) formation in apoA-I of HDL isolated from plasma of healthy control and type 1 diabetic subjects to assess apoA-I exposure to lipid peroxides and the status of oxidative stress in the vascular compartment in diabetes. Three tryptic peptides of apoA-I contain Met residues: Q(84)-M(86)-K(88), W(108)-M(112)-R(116), and L(144)-M(148)-R(149). These peptides and their Met(O) analogs were identified and quantified by mass spectrometry. Relative to controls, Met(O) formation was significantly increased at all three locations (Met(86), Met(112), and Met(148)) in diabetic patients. The increase in Met(O) in the diabetic group did not correlate with other biomarkers of oxidative stress, such as N(epsilon)-malondialdehyde-lysine or N(epsilon)-(carboxymethyl)lysine, in plasma or lipoproteins. The higher Met(O) content in apoA-I from diabetic patients is consistent with increased levels of lipid peroxidation products in plasma in diabetes. Using the methods developed here, future studies can address the relationship between Met(O) in apoA-I and the risk, development, or progression of the vascular complications of diabetes.

Advanced glycation end-products and methionine sulphoxide in skin collagen of patients with type 1 diabetes

We determined whether oxidative damage in collagen is increased in (1) patients with diabetes; (2) patients with diabetic complications; and (3) subjects from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, with comparison of subjects from the former standard vs intensive treatment groups 4 years after DCCT completion.

Nuclear magnetic resonance-determined lipoprotein subclass profile in the DCCT/EDIC cohort:associations with carotid intima-media thickness

To relate nuclear magnetic resonance lipoprotein subclass profiles (NMR-LSP) and other lipoprotein-related factors with carotid intima-media thickness (IMT) in Type 1 diabetes.

Effect of intensive glycemic control on levels of markers of inflammation in type 1 diabetes mellitus in the diabetes control and complications trial

Type 1 diabetes mellitus is associated with an increased risk of cardiovascular disease (CVD) that is not fully explained by conventional risk factors. The Diabetes Control and Complications Trial (DCCT) showed that intensive diabetes therapy reduced levels of LDL cholesterol and triglycerides but increased the risk of major weight gain, which might adversely affect CVD risk. The present study examined the effect of intensive therapy on levels of several markers of inflammation that have been linked to risk of CVD.

Nephropathy in a hypercholesterolemic mouse model with streptozotocin-induced diabetes

The contribution of preexisting hypercholesterolemia to diabetic nephropathy remains unclear. We assessed the impact of hypercholesterolemia on diabetic nephropathy using a double knockout (DKO) mouse, null for the low-density lipoprotein receptor (LDLRNDASH;/NDASH;) and the apoB mRNA editing catalytic polypeptide 1 (APOBEC1NDASH;/NDASH;).

Interaction of very-low-density lipoprotein isolated from type I (insulin-dependent) diabetic subjects with human monocyte-derived macrophages

Very-low-density lipoproteins (VLDL) (density less than 1.006 g/mL) were isolated from type I (insulin-dependent) diabetic patients in good to fair glycemic control and from age-, sex-, and race-matched, nondiabetic, control subjects. VLDL were incubated with human, monocyte-derived macrophages obtained from nondiabetic donors, and the rates of cellular cholesteryl ester synthesis and cholesterol accumulation were determined. VLDL isolated from diabetic patients stimulated significantly more cholesteryl ester synthesis than did VLDL isolated from control subjects (4.04 +/- 1.01 v 1.99 +/- 0.39 nmol 14C-cholesteryl oleate synthesized/mg cell protein/20 h; mean +/- SEM, P less than .05). The stimulation of cholesteryl ester synthesis in macrophages incubated with VLDL isolated from diabetic patients was paralleled by a significant increase in intracellular cholesteryl ester accumulation (P less than .05). The increase in cholesteryl ester synthesis and accumulation in macrophages were mediated by a significant increase in the receptor mediated, high affinity degradation (2.55 +/- 0.23 v 2.12 +/- 0.20 micrograms degraded/mg cell protein/20 h) and accumulation (283 +/- 35 v 242 +/- 33 ng/mg cell protein/20 h) of 125I-VLDL isolated from diabetic patients compared with VLDL from control subjects. To determine if changes in VLDL apoprotein composition were responsible for the observed changes in cellular rates of cholesteryl ester synthesis and accumulation, we also examined the apoprotein composition of the VLDL from both groups. There were no significant differences between the apoproteins B, E, and C content of VLDL from both groups. We also determined the chemical composition of VLDL isolated from both groups of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased serum pigment epithelium derived factor levels in Type 2 diabetes patients

Serum PEDF levels (mean (S.D.)) were increased in 96 Type 2 diabetic vs. 54 non-diabetic subjects; 5.3 (2.8) vs. 3.2 (2.0)mug/ml, p

Transmission of two novel mutations in a pedigree with familial lecithin:cholesterol acyltransferase deficiency:structure-function relationships and studies in a compound heterozygous proband

Two novel mutations were identified in a compound heterozygous male with lecithin:cholesterol acyltransferase (LCAT) deficiency. Exon sequence determination of the LCAT gene of the proband revealed two novel heterozygous mutations in exons one (C110T) and six (C991T) that predict non-conservative amino acid substitutions (Thr13Met and Pro307Ser, respectively). To assess the distinct functional impact of the separate mutant alleles, studies were conducted in the proband's 3-generation pedigree. The compound heterozygous proband had negligible HDL and severely reduced apolipoprotein A-I, LCAT mass, LCAT activity, and cholesterol esterification rate (CER). The proband's mother and two sisters were heterozygous for the Pro307Ser mutation and had low HDL, markedly reduced LCAT activity and CER, and the propensity for significant reductions in LCAT protein mass. The proband's father and two daughters were heterozygous for the Thr13Met mutation and also displayed low HDL, reduced LCAT activity and CER, and more modest decrements in LCAT mass. Mean LCAT specific activity was severely impaired in the compound heterozygous proband and was reduced by 50% in individuals heterozygous for either mutation, compared to wild type family members. It is also shown that the two mutations impair both catalytic activity and expression of the circulating protein.

A novel single base deletion in the LDLR gene (211delG):Effect on serum lipid profiles and the influence of other genetic polymorphisms in the ACE, APOE and APOB genes

A single base deletion (211delG) in the low density lipoprotein receptor (LDLR) gene was shown to cause familial hypercholesterolaemia (FH) in a large family from Northern Ireland. Twenty-four of 52 family members tested had this mutation, 13 of which were newly diagnosed. Mutation-positive individuals had significantly higher mean total-cholesterol (TC) and LDL-cholesterol (LDL-C) than those without 211delG. LDL-C was a more accurate indicator of disease status than TC, When TC levels alone were considered, in individuals over 16 years, a false negative rate (TC <7.5 mmol/l) of 40% was found; however, this fell to 13% based on inclusion of LDL-C levels. Individuals with coronary artery disease (CAD) had significantly higher TC levels than those without CAD and tended to have tendinous xanthomas (TX) and corneal arcus (CA). Genetic polymorphisms in the angiotensin converting enzyme (ACE) and apolipoprotein (ape) B genes did not appear to be associated with lipid levels or with the clinical severity of the disease; however, the apo E e4 allele did show a lipid-raising effect in individuals with the mutation.

High-density lipoprotein subfractions display proatherogenic properties in overweight and obese children

BACKGROUND: In adults, obesity-driven inflammation can lead to increased cardiovascular disease (CVD). However, information regarding childhood obesity and its inflammatory sequelae is less well defined. Serum amyloid-A (SAA) is an inflammatory molecule that rapidly associates with high-density lipoproteins (HDLs) and renders them dysfunctional. Therefore, SAA may be a useful biomarker to identify increased CVD potential in overweight and obese children.

METHODS: Young Hearts 2000 is a cross-sectional cohort study in which 92 children who were obese were matched for age and sex with 92 overweight and 92 lean children. HDL2 and HDL3 (HDL2&3) were isolated from plasma by a three-step rapid-ultracentrifugation procedure. SAA was measured in serum and HDL2&3 by an enzyme-linked immunosorbent assay procedure, and the activities of cholesterol ester transfer protein (CETP) and lecithin cholesteryl acyltransferase (LCAT) were measured by fluorimetric assays.

RESULTS: Trends across the groups indicated that SAA increased in serum and HDL2&3 as BMI increased, as did HDL2-CETP and HDL2-LCAT activities.

CONCLUSION: These results have provided evidence that overweight and obese children are exposed to an inflammatory milieu that impacts the antiatherogenic properties of HDL and that could increase CVD risk. This supports the concept that it is important to target childhood obesity to help minimize future cardiovascular events.

α-Tocopherol induces proatherogenic changes to HDL2 & HDL3: An in vitro and ex vivo investigation

Introduction: High density lipoproteins (HDL) have considerable potential for improving cardiovascular health. Additionally, epidemiological studies have identified an inverse relationship between a-tocopherol intake and cardiovascular disease, which has not been translated in randomised controlled trials. Objectives: This study assessed if increased α-tocopherol within HDL2 and HDL3 (HDL2&3) influenced their antiatherogenic potential. In the first of two in vitro investigations, the oxidation potential of HDL2&3 was assessed when α-tocopherol was added following their isolation. In the second, their oxidation potential was assessed when HDL2&3 were isolated from serum pre-incubated with α-tocopherol. Additionally, a 6-week placebo-controlled intervention with α-tocopherol assessed if α-tocopherol influenced the oxidation potential and activities of HDL2&3-associated enzymes, paraoxonase-1 (PON-1) and lecithin cholesteryl acyltransferase (LCAT). Results: Conflicting results arose from the in vitro investigations, whereby increasing concentrations of α-tocopherol protected HDL2&3 against oxidation in the post-incubated HDL2&3, and promoted HDL2&3-oxidation when they were isolated from serum pre-incubated with α-tocopherol. Following the 6-week placebo-controlled investigation, α-tocopherol increased in HDL2&3, while HDL2&3 became more susceptible to oxidation, additionally the activities of HDL2&3-PON-1 and HDL2-LCAT decreased. Conclusion: These results have shown for the first time that α-tocopherol induces changes to HDL2&3, which could contribute to the pathophysiology of cardiovascular disease.