Modulation of Nitric Oxide Production in Human Macrophages by Apolipoprotein-E and Amyloid-Beta Peptide

Vitek, Michael P.; Snell, Julie; Dawson, Hana N.; Colton, Carol A.

doi:10.1006/bbrc.1997.7408

Cited by 62 publications

(33 citation statements)

References 22 publications

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“…iNOS serves as a widely diffusible and long-lasting source of NO that is most commonly associated with activated immune cells such as microglia and astrocytes. Although contradictory data exist (44), it has been generally believed that A␤ peptides induce iNOS that increases NO and kills surrounding neurons (45). Microglia and astrocytes in AD brain, however, may not produce those pathological levels of NO associated with LPS injection into the brain or with acute immune stimulation (29,46,47).…”

Section: Discussionmentioning

confidence: 99%

NO synthase 2 ( NOS2 ) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease

Colton¹,

Vitek²,

Wink

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

123

103

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Section: Discussionmentioning

confidence: 99%

NO synthase 2 ( NOS2 ) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease

Colton¹,

Vitek²,

Wink

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

123

103

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“…Nitric oxide synthesized in smooth muscle cells can also inhibit their proliferation and reduce neointimal hyperplasia. 32 However, in the absence of apoE, a protein that has been shown to promote nitric oxide production in a variety of cell types, 16,22,34 the reduced capacity for nitric oxide synthesis may account for the contracted state and the exacerbated neointima in the vessel wall of the apoE Ϫ/Ϫ mice. The apparent vasoconstriction observed in the uninjured vessel wall of apoE Ϫ/Ϫ mice is supportive of the importance of apoE in maintaining vascular homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Both Apolipoprotein E and Immune Deficiency Exacerbate Neointimal Hyperplasia After Vascular Injury in Mice

Zhu

Reardon

Getz

et al. 2002

ATVB

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Abstract-In this study, we investigated the role of T and B lymphocytes in neointimal hyperplasia after endothelial denudation. Catheter-induced endothelial denudation of wild-type mice resulted in rapid infiltration of lymphocytes to the site of injury. Mice defective in recombination-activating gene 2 (RAG2 Ϫ/Ϫ ) showed increased neointimal formation 14 days after vascular injury in comparison to their wild-type immune-competent littermates. Immunohistochemical studies revealed the preponderance of smooth muscle cells and a significantly higher number of proliferating cells in the neointima of the RAG2 Ϫ/Ϫ mice. The neointima size and the number of proliferating smooth muscle cells in the injured vessel of RAG2 Ϫ/Ϫ mice were similar to those observed in the injured arteries of apolipoprotein E (apoE)-deficient (apoE Ϫ/Ϫ ) mice. Interestingly, mice with double apoE and RAG2 gene mutations (apoE Ϫ/Ϫ RAG2 Ϫ/Ϫ ) displayed similar neointimal characteristics as mice with a single gene defect, suggesting a similar mechanism for apoE and lymphocyte protection against injury-induced neointimal formation. The protective role of lymphocytes against neointimal formation after vascular injury directly contrasts to their reported role in the promotion of atherosclerosis, which was observed in both apoE ϩ/ϩ and apoE Ϫ/Ϫ mice. Thus, these results support the hypothesis of different etiology between hyperlipidemia-induced atherosclerosis and injury-induced vascular occlusion.

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“…B, immunoprecipitation of 35 S-labeled HUVEC membranes, with antipeptide antisera against the cytoplasmic insert of apoER2, verified that apoER2⌬4 -6 was expressed (130 kDa) and that a smaller amount of full-length apoER2 (180 kDa) was also present.…”

Section: Fig 6 Apoer2 Is Expressed In Huvecsmentioning

confidence: 95%

“…ApoE activates NOS III in platelets (11) and NOS II in macrophages (35). Because NO is a potent intracellular messenger and inhibitor of atherogenesis, in part by suppressing cytokine-induced VCAM-1 expression and reducing monocyte adherence to endothelium (26 -28), we investigated whether apoE might stimulate endothelial NO production.…”

Section: Fig 6 Apoer2 Is Expressed In Huvecsmentioning

confidence: 99%

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

Stannard¹,

Riddell²,

Sacre³

et al. 2001

Journal of Biological Chemistry

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Sub-endothelial infiltration of monocytes occurs early in atherogenesis and is facilitated by cell adhesion molecules that are up-regulated on activated endothelium. Apolipoprotein E (apoE) helps protect against atherosclerosis, in part, because apoE particles secreted by macrophages have local beneficial effects at lesion sites. Here, we hypothesize that such protection includes antiinflammatory actions and investigate whether cell-derived apoE can inhibit tumor necrosis factor-␣-mediated up-regulation of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Two models were used to mimic endothelial exposure to macrophage-derived apoE. In the first, HUVECs were transiently transfected to secrete apoE; VCAM-1 induction inversely correlated with secretion of apoE into the media (r ‫؍‬ ؊0.76, p < 0.001). In the second, incubation of HUVECs with media from recombinant Chinese hamster ovary (CHO) cells expressing apoE (CHO apoE ) also reduced VCAM-1 in a dose-dependent manner (r ‫؍‬ ؊0.70, p < 0.001). Characterization of CHO apoE cell-derived apoE revealed several similarities to apoE particles secreted by human blood monocyte-derived macrophages. The suppression of endothelial activation by apoE most likely occurs via stimulation of endothelial nitric oxide synthase; apoE increased levels of intracellular nitric oxide and its surrogate marker, cyclic guanosine monophosphate, while the nitric oxide synthase inhibitor, ethylisothiourea, blocked its effect. We propose that apoE secreted locally at lesion sites by macrophages may be anti-inflammatory by stimulating endothelium to release NO and suppress VCAM-1 expression.

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Modulation of Nitric Oxide Production in Human Macrophages by Apolipoprotein-E and Amyloid-Beta Peptide

Cited by 62 publications

References 22 publications

NO synthase 2 ( NOS2 ) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease

NO synthase 2 ( NOS2 ) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease

Both Apolipoprotein E and Immune Deficiency Exacerbate Neointimal Hyperplasia After Vascular Injury in Mice

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

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