Cell-derived Apolipoprotein E (ApoE) Particles Inhibit Vascular Cell Adhesion Molecule-1 (VCAM-1) Expression in Human Endothelial Cells

Stannard, Anita K.; Riddell, David; Sacre, Sandra; Tagalakis, Aristides D.; Langer, Claus; Eckardstein, Arnold von; Cullen, Paul; Athanasopoulos, Takis; Dickson, George; Owen, James S.

doi:10.1074/jbc.m104812200

Cited by 86 publications

(75 citation statements)

References 42 publications

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“…As the odds ratio and P value for e2 were not substantially different in the multiple logistic regression model compared with univariate analysis, we cannot rule out the possibility that the e2 allele may confer protection through other mechanisms. Thus, beyond an effect on lipid metabolism, apoE genotypes may also play additional roles in the development of CAD through inflammatory, antioxidant, and immune activities (4,43,44).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of apolipoprotein E2 on coronary artery disease in African Americans is mediated through lipoprotein cholesterol

Anuurad

Rubin

et al. 2006

Journal of Lipid Research

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We studied the relationship of apolipoprotein E (apoE) isoforms and coronary artery disease (CAD) in 224 African Americans and 326 Caucasians undergoing diagnostic coronary angiography. The presence of CAD was defined as .50% stenosis in at least one artery. ApoE allele frequencies were 0.12, 0.62, and 0.26 for e2, e3, and e4, respectively, in African Americans and 0.08, 0.78, and 0.14 for e2, e3, and e4, respectively, in Caucasians. Among African Americans, CAD was present in 9 of 34 e2 carriers (26%), significantly smaller (P , 0.05) in proportion compared with 39 of 82 e3 carriers and 43 of 92 e4 carriers (48% and 47%, respectively), suggesting a protective effect of the e2 allele. No such difference was seen in Caucasians. In African Americans but not Caucasians, LDL cholesterol was lower in e2 carriers than in e3 and e4 carriers (106 vs. 127 and 134 mg/dl, respectively; P , 0.005). After adjusting for lipid levels, the association between apoE2 and CAD was no longer significant. Thus, the protective effect of apoE2 seen in African Americans could be explained by a favorable lipid profile in e2 carriers, whereas in Caucasians, the absence of such a protective effect could be attributable to the lack of effect of apoE2 on the lipid

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Section: Discussionmentioning

confidence: 99%

Protective effect of apolipoprotein E2 on coronary artery disease in African Americans is mediated through lipoprotein cholesterol

Anuurad

Rubin

et al. 2006

Journal of Lipid Research

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“…In excess, however, it is volatile and reacts rapidly with superoxide to form peroxynitrite, a potential mediator of cyto-and neurotoxicity by nitration of amino acids and oxidation of lipids, proteins and DNA [25,26]. We have previously shown in platelets [27] and endothelial cells [28] that binding of apoE by one of its receptors, apoE receptor 2 (apoER2), can initiate a signalling cascade which upregulates endothelial nitric oxide synthase (NOS3) activity and NO production. Furthermore, this effect is isoformdependent with apoE4 releasing much less NO than apoE3 [29].…”

Section: Introductionmentioning

confidence: 99%

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

Thilakawardhana

Everett

Murdock

et al. 2005

Neurobiology of Aging

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Apolipoprotein (apo) E4 is a risk factor for Alzheimer's disease, compared to wild-type apoE3. The mechanism(s) is unknown. One possibility, demonstrated in peripheral tissue cell lines, is that apoE stimulates nitric oxide synthase (NOS) via a receptor-dependent signalling pathway and that apoE4 generates inappropriate amounts of NO compared to apoE3. Prior to biochemical investigations, we have quantified the expression of several candidate receptor genes, including low-density lipoprotein (LDL)-receptor family members and scavenger receptor class B, types I and II (SR-BI/II), as well as the three NOS isoenzymes and protein kinase B (Akt), in 38 human cell lines, of which 12 derive from brain. Expression of apoE receptor 2 (apoER2), a known signalling receptor in brain, was readily detected in SH-SY-5Yand CCF-STTG1 cells, common models of neurons and astrocytes, respectively, and was highest in H4 neuroglioma and IMR-32 neuroblastoma cells. Transcripts of the other lipoprotein receptors were widely, but variably, distributed across the different cell types. Of particular note was the predominant expression of SR-BII over SR-BI in many of the brainderived cells. As the C-terminus of SR-BII, like apoER2, contains potential SH3 signalling motifs, we suggest that in brain SR-BII functions as a signal transducer receptor.

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“…In macrophages, the endogenous expression of apoE functions primarily to facilitate lipid flux (11,12). However, macrophage-derived apoE in the arterial wall has also been associated with local anti-inflammatory and antioxidant effects (13)(14)(15). ApoE is also highly expressed in hepatocytes and steroidogenic cells (16 -18).…”

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confidence: 99%

Oxidative Stress Regulates Adipocyte Apolipoprotein E and Suppresses Its Expression in Obesity

Espiritu

Mazzone

2008

Diabetes

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OBJECTIVE— Endogenous expression of apolipoprotein E (apoE) has a significant impact on adipocyte lipid metabolism and is markedly suppressed in obesity. Adipose tissue oxidant stress is emerging as an important mediator of adipocyte dysfunction. These studies were undertaken to evaluate the role of oxidant stress for regulation of adipocyte apoE. RESEARCH DESIGN AND METHODS— ApoE gene and protein expression in 3T3-L1 adipocytes or mature adipocytes and adipose tissue from C57/BL6 mice was evaluated after induction of oxidant stress. The response of adipose tissue and adipocytes from obese compared with lean mice to antioxidants was also assessed. RESULTS— Oxidant stress in 3T3-L1 cells or adipocytes and adipose tissue from lean mice significantly reduced apoE mRNA and protein level. Inclusion of an antioxidant eliminated this reduction. Oxidant stress was accompanied by activation of the nuclear factor-κB (NF-κB) transcription complex, and its effect on apoE was eliminated by an NF-κB activation inhibitor. Treatment of freshly isolated adipose tissue or mature adipocytes from obese mice with antioxidant increased apoE expression but had no effect on cells or tissue from lean mice. Incubation of freshly isolated adipocytes from lean mice with stromovascular cells from obese mice significantly suppressed adipocyte apoE compared with incubation with stromovascular cells from lean mice, but this suppression was reversed by inclusion of antioxidant or a neutralizing antibody to tumor necrosis factor-α. CONCLUSIONS— Oxidant stress significantly modulates adipose tissue and adipocyte apoE expression. Furthermore, oxidant stress contributes to suppression of adipocyte apoE in obesity. This suppression depends on interaction between adipose tissue stromovascular cells and adipocytes.

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Cell-derived Apolipoprotein E (ApoE) Particles Inhibit Vascular Cell Adhesion Molecule-1 (VCAM-1) Expression in Human Endothelial Cells

Cited by 86 publications

References 42 publications

Protective effect of apolipoprotein E2 on coronary artery disease in African Americans is mediated through lipoprotein cholesterol

Protective effect of apolipoprotein E2 on coronary artery disease in African Americans is mediated through lipoprotein cholesterol

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

Oxidative Stress Regulates Adipocyte Apolipoprotein E and Suppresses Its Expression in Obesity

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