Apolipoprotein E - A Multifunctional Protein with Implications in Various Pathologies as a Result of Its Structural Features

Tudorache, I.F.; Trusca, Violeta Georgeta; Gafencu, Anca Violeta

doi:10.1016/j.csbj.2017.05.003

Cited by 144 publications

(116 citation statements)

References 110 publications

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“…NO-dependent atheroprotective effects of HDL enzyme, i.e., PON1 were implied by a study in which HDL isolated from PON1-deficient mice failed to stimulate NO production in mouse aortic endothelial cells [35,42]. Apart from the aforementioned apoA-I and PON-1, other HDL-associated apolipoproteins (e.g., ApoE) are also responsible for antioxidant effects of HDL particles [43,44]. For example, apoE2 was shown to stimulate endothelial NO release and apoE4, to exert proinflammatory effects, whereas apoA-IV showed antiatherosclerotic, anti-inflammatory, and antioxidant actions in vivo [45][46][47][48].…”

Section: Hdl Role and Functionsmentioning

confidence: 99%

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease

Rysz

Gluba-Brzózka

Rysz-Górzyńska

et al. 2020

IJMS

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Chronic kidney disease (CKD) is a worldwide health problem with steadily increasing occurrence. Significantly elevated cardiovascular morbidity and mortality have been observed in CKD. Cardiovascular diseases are the most important and frequent cause of death of CKD patients globally. The presence of CKD is related to disturbances in lipoprotein metabolism whose consequences are dyslipidemia and the accumulation of atherogenic particles. CKD not only fuels the reduction of high-density lipoprotein (HDL) cholesterol concentration, but also it modifies the composition of this lipoprotein. The key role of HDL is the participation in reverse cholesterol transport from peripheral tissues to the liver. Moreover, HDL prevents the oxidation of low-density lipoprotein (LDL) cholesterol by reactive oxygen species (ROS) and protects against the adverse effects of oxidized LDL (ox-LDL) on the endothelium. Numerous studies have demonstrated the ability of HDL to promote the production of nitric oxide (NO) by endothelial cells (ECs) and to exert antiapoptotic and anti-inflammatory effects. Increasing evidence suggests that in patients with chronic inflammatory disorders, HDLs may lose important antiatherosclerotic properties and become dysfunctional. So far, no therapeutic strategy to raise HDL, or alter the ratio of HDL subfractions, has been successful in slowing the progression of CKD or reducing cardiovascular disease in patients either with or without CKD.

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Section: Hdl Role and Functionsmentioning

confidence: 99%

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease

Rysz

Gluba-Brzózka

Rysz-Górzyńska

et al. 2020

IJMS

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“…APOE is a widely expressed multifunctional, low‐density lipoprotein receptor ligand that primarily serves as a lipid transporter . It also serves as an antioxidant and a regulator of immune and inflammatory responses . IGHG1 is the most common immunoglobulin G protein and an important component of immunological antibodies .…”

Section: Discussionmentioning

confidence: 99%

Reduced expression of apolipoprotein E and immunoglobulin heavy constant gamma 1 proteins in Fuchs endothelial corneal dystrophy

Kuot

Ronci

Mills

et al. 2019

Clinical Exper Ophthalmology

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Background Fuchs endothelial corneal dystrophy (FECD) is a progressive and potentially a sight threatening disease, and a common indication for corneal grafting in the elderly. Aberrant thickening of Descemet's membrane, formation of microscopic excrescences (guttae) and gradual loss of corneal endothelial cells are the hallmarks of the disease. The aim of this study was to identify differentially abundant proteins between FECD‐affected and unaffected Descemet's membrane. Methods Label‐free quantitative proteomics using nanoscale ultra‐performance liquid chromatography‐mass spectrometry (nUPLC‐MSE) was employed on affected and unaffected Descemet's membrane extracts, and interesting findings were further investigated using quantitative reverse transcription‐polymerase chain reaction and immunohistochemical techniques. Results Quantitative proteomics revealed significantly lower abundance of apolipoprotein E (APOE) and immunoglobulin heavy constant gamma 1 protein (IGHG1) in affected Descemet's membrane. The difference in the distribution of APOE between affected and unaffected Descemet's membrane and of IGHG1 detected by immunohistochemistry support their down‐regulation in the disease. Comparative gene expression analysis showed significantly lower APOE mRNA levels in FECD‐affected than unaffected corneal endothelium. IGHG1 gene is expressed at extremely low levels in the corneal endothelium, precluding relative expression analysis. Conclusions This is the first study to report comparative proteomics of Descemet's membrane tissue, and implicates dysregulation of APOE and IGHG1 proteins in the pathogenesis of Fuchs endothelial corneal dystrophy.

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“…In addition, one of these metabolites, Cglycosyltryptophan, was associated with age-related traits including bone mineral density, lung (30) and kidney function (35). (ii) As expected from APOE's known role in cholesterol and lipid metabolism (36,37), common genetic variants in this gene were associated with blood cholesterol levels in genome-and metabolome-wide association studies (37,38). In addition, associations with levels of various SMs were identified (39,40).…”

Section: Introductionmentioning

confidence: 92%

The Alzheimer’s Disease Metabolome: Effects of Sex andAPOEε4 genotype

Arnold¹,

Nho²,

Kueider‐Paisley³

et al. 2019

Preprint

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Research provides substantial evidence that late-onset Alzheimer's disease (AD), the major cause of dementia in the elderly, is a metabolic disease. Besides age, female sex and APOEε4 genotype represent strong risk factors for AD, and at the same time, give rise to large metabolic differences. Our systematic investigation of sex and APOE ε4 genotype differences in the link between metabolism and measures of pre-symptomatic AD using stratified analysis revealed several group-specific metabolic alterations that were not observed without sex and genotype stratification of the same cohort. Pathways linked to the observed metabolic alterations suggest females are more affected by impairment of mitochondrial energy production in AD than males, highlighting the importance of tailored treatment approaches towards a precision medicine approach. AbstractRecent studies have provided evidence that late-onset Alzheimer's disease (AD), the major cause of dementia in the elderly, can, at least in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 genotype represent strong risk factors for AD. At the same time, they both give rise to large metabolic differences, suggesting that metabolic aspects of AD pathogenesis may differ between males and females and APOE ε4 carriers and non-carriers, respectively. Here, we systematically investigated group-specific metabolic alterations by conducting stratified association analyses of 140 metabolites measured in serum samples of 1,517 individuals from the AD neuroimaging initiative with AD biomarkers for Aβ and tau pathology, as well as neurodegeneration. We observed substantial sex differences in effects of 15 metabolites on AD biomarkers with partially overlapping differences for APOE ε4 status groups. These metabolites highlighted several group-specific alterations that were not observed in unstratified analyses using sex and APOE ε4 as covariates. Combined stratification by both variables uncovered further subgroup-specific metabolic effects limited to the group with presumably highest AD risk, i.e. APOE ε4+ females. Pathways linked to the observed metabolic alterations suggest that females experience more expressed impairment of mitochondrial energy production in AD than males. These findings indicate that dissecting metabolic heterogeneity in AD pathogenesis may allow for grading the biomedical relevance of specific pathways for specific subgroups. Extending our approach beyond simple one or two-fold stratification may thus guide the way to personalized medicine. Alzheimer's Association; Alzheimer's Drug Fund and the Karen L. Wrenn Trust. PMD has served as an advisor to and or received grants from companies for other projects. PMD also owns shares or serves on the board of companies whose products are not discussed here. PMD is also a co-inventor on patents in this field through Duke University which are unlicensed.

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Apolipoprotein E - A Multifunctional Protein with Implications in Various Pathologies as a Result of Its Structural Features

Cited by 144 publications

References 110 publications

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease

Reduced expression of apolipoprotein E and immunoglobulin heavy constant gamma 1 proteins in Fuchs endothelial corneal dystrophy

The Alzheimer’s Disease Metabolome: Effects of Sex andAPOEε4 genotype

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