ApoE

Vibrio cholerae, the causative pathogen of the life-threatening infection cholera, encodes two copies of β-ketoacyl-ACP synthase III (vcFabH1 and vcFabH2). vcFabH1 and vcFabH2 are pathogenic proteins associated with fatty acid synthesis, lipid metabolism, and potential applications in biofuel production. Our biochemical assays characterize vcFabH1 as exhibiting specificity for acetyl-CoA and CoA thioesters with short acyl chains, similar to that observed for FabH homologs found in most Gram-negative bacteria...

Aims: Oxidative stress and inflammation play an important role in the progression of atherosclerosis. Transcription factor NF-E2-related factor 2 (Nrf2) has antioxidant and anti-inflammatory effects in the vessel wall, but paradoxically, global loss of Nrf2 in apoE deficient mice alleviates atherosclerosis. In this study, we investigated the effect of global Nrf2 deficiency on early and advanced atherogenesis in alternative models of atherosclerosis, LDL receptor deficient mice (LDLR-/-) and LDLR-/- mice expressing apoB-100 only (LDLR-/-ApoB100/100) having a humanized lipoprotein profile...

Lipoproteins (LPs) are a set of naturally occurring bio-nanoparticles consisting of Apo-LPs, phospholipids, a highly hydrophobic core of cholesteryl esters and triglycerides that participate mainly in the targeted transport of cholesteryl esters and other hydrophobic molecules through the bloodstream. They also are able to recognize specific receptors on normal and abnormal cells. Therefore, LPs represent a relevant tool for targeted delivery of cancer diagnostics and therapeutics due to their native biocompatibility, biodegradability, nano-scale size and receptor-mediated uptake...

In this study, a commercial uniform field drift tube ion mobility-mass spectrometer (IM-MS) was utilized to measure the gas-phase conformational populations of three well-studied proteins: ubiquitin (8566 Da), cytochrome c (12,359 Da), and myoglobin in both apo and holo forms (16,951 and 17,567 Da, respectively) in order to evaluate the use of this technology for broadscale structural proteomics applications. Proteins were electrosprayed from either acidic organic (pH ~3) or aqueous buffered (pH ~6.6) solution phase conditions, which generated a wide range of cation charge states corresponding to both extended (unfolded) and compact (folded) gas-phase conformational populations...

BACKGROUND AND AIMS: Pre-eclampsia constitutes a leading cause of maternal and perinatal morbidity and mortality. Pre-eclampsia susceptibility is believed to be associated with altered lipid profiles and abnormal lipid metabolism via lipid peroxidation that leads to endothelial dysfunction. The goal of this study was to evaluate the association of maternal blood lipid and apolipoprotein levels with pre-eclampsia in a large-scale study. METHODS: Using data from a large case-control study (1366 cases of pre-eclampsia and 1741 normotensive controls), the association between the distributions of eight lipid fractions and pre-eclampsia risk was evaluated using adjusted logistic regression models...

BACKGROUND: A dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases. These diseases often show a sex bias, suggesting sex differences in immune responses and in the intestinal microbiome. We hypothesized that sex differences in immune responses are associated with sex differences in microbiota composition. METHODS: Fecal microbiota composition (MITchip), mRNA expression in intestinal tissue (microarray), and immune cell populations in mesenteric lymph nodes (MLNs) were studied in male and female mice of two mouse strains (C57B1/6OlaHsd and Balb/cOlaHsd)...

We investigated the associations of genetic risk score (GRS) for Alzheimer's disease and apolipoprotein E (APOE) ɛ variant with cardiometabolic risk factors during 2-year follow-up in children and whether body fat percentage (BF%) modify these associations. A population-based sample of 469 children (246 boys, 223 girls) at baseline and 398 children (201 boys, 197 girls) at 2-year follow-up participated in the study. Genotyping was performed using the the Illumina Custom Infinium CardioMetabo BeadChip and the Illumina Infinium HumanCoreExome BeadChip...

BACKGROUND: Early Alzheimer's disease (AD) detection using cerebrospinal fluid (CSF) biomarkers has been recommended as enrichment strategy for trials involving mild cognitive impairment (MCI) patients. OBJECTIVE: To model a prodromal AD trial for identifying MRI structural biomarkers to improve subject selection and to be used as surrogate outcomes of disease progression. METHODS: APOE ɛ4 specific CSF Aβ42/P-tau cut-offs were used to identify MCI with prodromal AD (Aβ42/P-tau positive) in the WP5-PharmaCog (E-ADNI) cohort...

BACKGROUND: A 3-year extension of two Phase III parent studies of intravenous (IV) bapineuzumab in patients with mild-to-moderate Alzheimer's disease dementia (apolipoprotein (APOE) ɛ4 carriers and noncarriers) is summarized. OBJECTIVES: The primary and secondary objectives were to evaluate the long-term safety, tolerability, and maintenance of efficacy of bapineuzumab. METHODS: A multicenter study in patients who had participated in double-blind placebo-controlled parent studies...

BACKGROUND/AIMS: Hypertriglyceridaemia (HTG) and reduction and dysfunction of high density lipoprotein (HDL) are common lipid disturbances in chronic kidney disease (CKD). HTG in CKD is caused mainly by the decreased efficiency of lipoprotein lipase (LPL)-mediated very low density lipoprotein triglyceride (VLDL-TG) lipolysis. It has not been clarified whether HDL dysfunction in CKD contributes directly to HTG development; thus, the aim of this study was to assess the impact of CKD progression on the ability of HDL to enhance LPL-mediated VLDL-TG lipolysis efficiency...

OBJECTIVE: The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for late-onset Alzheimer's disease. Many ε4 carriers, however, never develop Alzheimer's disease. The purpose of this study is to characterize the variability in phenotypic expression of the ε4 allele, as measured by the longitudinal trajectory of cognitive test scores and MRI brain volumes, in cognitively intact elders. METHOD: Healthy older adults, ages 65-85, participated in a 5-year longitudinal study that included structural MRI and cognitive testing administered at baseline and at 1...

African Americans are 1.4 times more likely than European Americans to carry the apolipoprotein E (APOE) ε4 allele, a risk factor for Alzheimer's disease (AD). However, little is known about the neural correlates of cognitive function in older African Americans and how they relate to genetic risk for AD. In particular, no past study on African Americans has examined the effect of APOE ε4 status on pattern separation-mnemonic discrimination performance and its corresponding neural computations in the hippocampus...

An apolipoprotein E ε4 (APOE-ε4) genotype is the strongest common genetic determinant of Alzheimer's disease (AD). The pleiotropic nature of apolipoprotein E has made elucidation of the aetiological basis difficult to establish, which is further complicated by the fact that the penetrance of the APOE-ε4 allele is modulated by sex, age, and nutrition. A greater metabolic consequence of the APOE-ε4 allele is likely to contribute to the fact that two-thirds of AD patients are female. A higher tissue status of the marine n-3 fatty acid docosahexaenoic acid (DHA) is associated with a lower AD risk...

Human porphobilinogen deaminase (PBGD), the third enzyme in the heme pathway, catalyzes four times a single reaction to convert porphobilinogen into hydroxymethylbilane. Remarkably, PBGD employs a single active site during the process, with a distinct yet chemically equivalent bond formed each time. The four intermediate complexes of the enzyme have been biochemically validated and they can be isolated but they have never been structurally characterized other than the apo- and holo-enzyme bound to the cofactor...

Zinc oxide nanoparticles (ZnO) are presented as potential cancer therapeutic agent based on their surface properties. In this study, the most abundant blood proteins, albumin, fibrinogen and apo-transferrin, were covalently bound (c-ZnO NPs) and nonspecifically adsorbed (n-ZnO NPs) onto ZnO NPs to evaluate the role of modification route on protein structure and their effects on glioblastoma cells. The success of modification and structures of proteins on ZnO NPs were characterized with FT-IR. It was found that non-covalent interaction significantly damaged the secondary structure of proteins compared to those covalently attached to the ZnO nanoparticle...

We report the genetic analysis of a "humanized" hyperlipidemic mouse model for progressive nonalcoholic steatohepatitis (NASH) and fibrosis. Mice carrying transgenes for human APOE*3-Leiden and CETP and fed a "Western" diet were studied on the genetic backgrounds of over 100 inbred mouse strains. The mice developed hepatic inflammation and fibrosis that was highly dependent on genetic background, with vast differences in the degree of fibrosis. Histological analysis showed features characteristic of human NASH, including macrovesicular steatosis, hepatocellular ballooning, inflammatory foci and pericellular collagen deposition...

To evaluate the presence of serum protein biomarkers associated with the early phases of formation of carotid atherosclerotic plaques, label-free quantitative proteomics analyses were made for serum samples collected as part of The Cardiovascular Risk in Young Finns Study. Samples from subjects who had an asymptomatic carotid artery plaque detected by ultrasound examination (N = 43, Age = 30-45 years) were compared with plaque free controls (N = 43) (matched for age, sex, body weight and systolic blood pressure)...

We previously discovered that oral treatment with AC261066, a synthetic selective agonist for the retinoic acid β2-receptor (RARβ2), decreases oxidative stress in the liver, pancreas, and kidney of mice fed a high-fat diet (HFD). Since hyperlipidemic states are causally associated with myocardial ischemia and oxidative stress, we have now investigated the effects of AC261066 in an ex-vivo ischemia/reperfusion (I/R) injury model in hearts of two prototypic dysmetabolic mice. We found that a 6-week oral treatment with AC261066 in both genetically hypercholesterolemic (ApoE-/-) and obese (HFD-fed) wild-type mice exerts protective effects when their hearts are subsequently subjected to I/R ex vivo in the absence of added drug...

BACKGROUND: Atherosclerosis is a slowly progressing, chronic multifactorial disease characterized by the accumulation of lipids, inflammatory cells, and fibrous tissue that drives to the formation of asymmetric focal thickenings in the tunica intima of large and mid-sized arteries. Despite the high therapeutic potential of ApoA-1 proteins, the purification and delivery into the disordered organisms of these drugs is still limited by low efficiency in these processes. METHODS AND RESULTS: We report here a novel production and delivery system of anti-atherogenic APOA-1Milano muteins (APOA-1M) by means of genetically modified rice plants...

Atherosclerosis (AS) is the key cause of many cardiovascular and cerebrovascular diseases. The inflammatory response and lipid metabolism disorders contribute to the development and progression of AS. This work aims to study the anti-inflammatory effect and mechanism of low molecular weight fucoidan (LMWF) obtained from Saccharina japonica on atherosclerosis in apoE-knockout mice. The experimental results showed that LMWF statistically decreased the levels of triglyceride (TRIG) and oxidative low-density lipoproteins (ox-LDL) and stabilized established atherosclerotic lesions...