Elena Fuior

Elena Fuior
Nicolae Simionescu Institute of Cellular Biology and Pathology | ICBP · Gene Regulation

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32
Publications
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416
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Publications

Publications (32)
Article
Full-text available
The receptor for advanced glycation end products (RAGE) plays a central role in the chronic inflammatory process associated with atherosclerosis development. We aimed to develop lipoplexes carrying RAGE-short hairpin (sh) RNA, targeted to the adhesion molecule P-selectin, selectively expressed on the surface of activated endothelium (Psel-lipo/shRA...
Article
Full-text available
Naringenin, an anti-inflammatory citrus flavonoid, is restrained from large-scale use by its reduced water solubility and bioavailability. To overcome these limitations, naringenin was loaded into lipid nanoemulsions directed towards vascular cell adhesion molecule (VCAM)-1, exposed by activated endothelium, and delivered intravenously in a murine...
Article
Full-text available
Calcific aortic valve disease (CAVD) is a progressive disorder that increases in prevalence with age. An important role in aortic valve calcification is played by valvular interstitial cells (VIC), that with age or in pathological conditions acquire an osteoblast-like phenotype that advances the disease. Therefore, pharmacological interventions aim...
Chapter
A chronic inflammatory process is involved in numerous diseases, including cardiovascular diseases, diabetes, cancer, autoimmune, and neurodegenerative diseases. Lately, a special attention was focused on the development of new nanoparticle-based therapies to directly target the inflammation and release bioactive compounds with antiinflammatory pro...
Article
Full-text available
Apolipoprotein C1 (apoC1), the smallest of all apolipoproteins, participates in lipid transport and metabolism. In humans, APOC1 gene is in linkage disequilibrium with APOE gene on chromosome 19, a proximity that spurred its investigation. Apolipoprotein C1 associates with triglyceride-rich lipoproteins and HDL and exchanges between lipoprotein cla...
Article
Full-text available
Citrus flavonoids have well-documented protective effects on cardiovascular system, but the poor water solubility and reduced bioavailability restrict their therapeutic use. We aimed to overcome these limitations and encapsulated naringenin and hesperetin into lipid nanoemulsions (LNs), targeted to vascular cell adhesion molecule-1 (VCAM-1), which...
Article
Full-text available
Apolipoprotein E (apoE) is mainly secreted by hepatocytes and incorporated into most plasma lipoproteins. Macrophages, which accumulate cholesterol and are critical for the development of the atherosclerotic plaque, are also an important, albeit smaller, apoE source. Distal regulatory elements control cell-specific activity of the apoE promoter: mu...
Article
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: The progress in small-interfering RNA (siRNA) therapeutics depends on the development of suitable nanocarriers to perform specific and effective delivery to dysfunctional cells. In this paper, we questioned whether P-selectin, a cell adhesion molecule specifically expressed on the surface of activated endothelial cells (EC) could be employed as a...
Article
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In the present study we aimed to evaluate the potential of in vivo inhibition of miR-486 and miR-92a to reverse hyperlipidemia, then to identify and validate their lipid metabolism-related target genes. Male Golden-Syrian hamsters fed a hyperlipidemic (HL) diet (standard chow plus 3% cholesterol and 15% butter, 10 weeks) were injected subcutaneousl...
Article
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Lissencephaly-1 (Lis1) protein is a dynein-binding protein involved in neural stem cell division, morphogenesis and motility. To determine whether Lis1 is a key factor in glioblastoma, we evaluated its expression and function in CD133+ glioblastoma cells. Global, Lis1 gene expression is similar in glioblastoma and normal samples. Interestingly, imm...
Article
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Apolipoprotein E (apoE) has anti-atherosclerotic properties, being involved in the transport and clearance of cholesterol-rich lipoproteins as well as in cholesterol efflux from cells. We hypothesized that glucocorticoids may exert anti-inflammatory properties by increasing the level of macrophage-derived apoE. Our data showed that glucocorticoids...
Article
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Certain TCF7L2 (T-cell factor 7-like2 transcription factor) gene polymorphisms render significant susceptibility for type 2 diabetes mellitus (T2DM). TCF7L2 rs7903146 and rs290487 are single nucleotide gene polymorphisms whose association with T2DM was demonstrated in several ethnic groups. The aim of the study was to analyze for the first timethe...
Article
Introduction Recent evidences show a key role for Lis1 in hematopoietic stem cells function and leukemogenesis by regulating the asymmetric division and self-renewal of stem cell population. Moreover, Lis1 is involved in neural progenitor cell migration. Therefore, we investigated Lis1 expression in CD133+ glioblastoma cells and evaluated its possi...
Article
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Aim: To investigate the effect of high homocysteine (Hcy) levels on apolipoprotein E (apoE) expression and the signaling pathways involved in this gene regulation. Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot were used to assess apoE expression in cells treated with various concentrations (50-500 μmol/L) of...
Article
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Atherosclerosis is a multistage disease promoted by cholesterol accumulation in the macrophages recruited in the subendothelial space. Despite the fact that apolipoprotein E (ApoE) released by infiltrated macrophages promotes cholesterol efflux, this process is not sufficient to preclude the progression of atherogenesis, especially since apoE gene...
Article
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Apolipoprotein E (APOE) is a lipid transport protein which remarkably illustrates the structurefunction paradigm through the isoform-specific effects it exerts in cardiovascular, neurological and immune pathologies. In the brain, APOE is mostly involved in cholesterol redistribution from the astrocytes to the neurons. However, APOE affects also oth...
Article
Full-text available
Apolipoprotein E(apoE) has an important role in directing lipid transport from peripheral tissues to the liver. Among human apoE isoforms, apoE3 is considered to be atheroprotective. In atheroma, macrophages-derived apoE is downregulated under inflammatory conditions. Endothelial cells (ECs), an important component of the atherosclerotic plaque, do...
Article
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Atherosclerosis and its complications represent the leading death cause worldwide, despite many therapeutic developments. Atherosclerosis is a complex, multi-stage disease whereby perturbed lipid metabolism leads to cholesterol accumulation into the vascular walls and plaque formation. Generation of apoE-/- and LDLR-/- atherosclerosis mouse models...
Article
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Translin and translin-associated factor X are two highly conserved proteins with nucleic acid binding activities, which are considered to act as a sensor for cell survival and proliferation in various normal and stress-related conditions. Despite the progresses made in the characterization of their function, their physiological role is still elusiv...
Article
Atherosclerosis, a prime cause of mortality across the developed societies, was targeted by diverse therapeutic strategies. These evolved in response to the complex etiology and evolution of the disease. Many enzymes are associated with atherosclerosis, either in the main stream of lipid biosynthesis and transport or in the collateral and intertwin...
Article
Full-text available
In atherogenesis, macrophage-derived apolipoprotein E (apoE) has an athero-protective role by a mechanism that is not fully understood. We investigated the regulatory mechanisms involved in the modulation of apoE expression in macrophages. The experiments showed that the promoters of all genes of the apoE/apoCI/apoCIV/apoCII gene cluster are enhanc...
Article
Full-text available
The atheroprotective role of apolipoprotein E (apoE) is well established. During inflammation, expression of apoE in macrophages is reduced leading to enhanced atheromatous plaque development. In the present study, we investigated the signaling pathways involved in the repression of apoE gene expression in response to lipopolysaccharide (LPS) treat...
Article
Translin is an octameric single-stranded DNA binding protein consisting of 228 amino acid residues per monomer. This protein contains two cysteine residues per monomer. Studies of reactions with DTNB show that both cysteines are reactive and exhibit biphasic reaction kinetics. Further studies with two site-directed mutants, C58S and C225S, confirm...
Article
Translin is a recently identified nucleic acid binding protein that appears to be involved in the recognition of conserved sequences found at many chromosomal breakpoints. Previous reports indicate that, based on gel filtration analysis and electron microscopy of protein-DNA complexes, translin forms an octameric structure that binds the DNA. In th...
Article
Full-text available
Platelet-derived growth factor (PDGF) and serum, but not epidermal growth factor (EGF), stimulated sphingosine kinase activity in Swiss 3T3 fibroblasts and increased intracellular concentrations of sphingosine 1-phosphate (SPP), a sphingolipid second messenger (Olivera, A., and Spiegel, S. (1993) Nature 365, 557-560). We report herein that DL-threo...
Chapter
Homeostasis of multicellular organisms as well as their normal development depends on the balance between cellular proliferation, differentiation, and cell death or apoptosis. Ceramide, sphingosine, and sphingosine-1-phosphate (SPP), metabolites of sphingolipids, and ubiquitous components of eukaryotic cell membranes, have recently emerged as membe...
Chapter
Full-text available
Sphingolipid metabolites have been suggested to play an important role in cellular signaling. Branching pathways of sphingolipid metabolism may regulate either apoptosis or mitogenic effects depending on the cell type and the nature of the stimulus. Ceramide produced by sphingomyelinase activation has been shown to induce apoptosis and cell growth...

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Projects (2)
Project
Atherosclerosis is an inflammatory disease, generated and/or aggravated by lipid metabolism disorders. The discovery of microRNAs (miRNAs) and their role in the regulation of the gene expression is one of the most exciting scientific breakthroughs of the last period. Identifying functional miRNA target genes is crucial to understand cellular function of specific miRNAs. Our preliminary results show that miR-486 and miR-92a are significantly associated with coronary artery disease (CAD) vulnerability and are associated primarily with high density lipoproteins (HDL), specifically with HDL2 and HDL3. Existing data do not refer to the existence of lipid metabolism-related genes that are functionally targeted by miR-486 and miR-92a, although these miRNAs individually target over 250 genes. The main aim of the project is to evaluate molecular therapy for dyslipidaemia by in vivo modulation of microRNAs expression. Our working hypothesis is that dyslipidemia may be treated by using specific inhibition of miRNAs. Accordingly, the first objective is to identify by bioinformatics analysis and to validate lipid metabolism-related genes targeted by miR-486 and miR-92a. We will further explore blood and tissue-specific microarray distribution of miRNAs in hyperlipidemic animals. Furthermore, we will evaluate the effects of in vivo inhibition of miRNAs in atherosclerosis development. Finally, we will assess the HDL-mediated transfer of specific microRNAs to cultured cells.