Phenotypic Heterogeneity of the Endothelium

Aird, William C.

doi:10.1161/01.res.0000255691.76142.4a

Cited by 1,486 publications

(929 citation statements)

References 182 publications

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“…The endothelium plays a pivotal role in the homeostasis of tissues and small changes in the function of ECs might impact the functionality of organs or even the health of an entire organism. 15 In addition to examining toxic effects, an evaluation of PEGylated AuNPs on EC pro-inflammatory induction is necessary. An increased expression of cell adhesion molecules leads to leukocyte adhesion to the activated endothelium and results in transmigration into the tissue.…”

Section: Introductionmentioning

confidence: 99%

Gold nanoparticle interactions with endothelial cells cultured under physiological conditions

et al. 2017

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a PEGylated gold nanoparticles (AuNPs) have an extended circulation time after intravenous injection in vivo and exhibit favorable properties for biosensing, diagnostic imaging, and cancer treatment. No impact of PEGylated AuNPs on the barrier forming properties of endothelial cells (ECs) has been reported, but recent studies demonstrated that unexpected effects on erythrocytes are observed. Almost all studies to date have been with static-cultured ECs. Herein, ECs maintained under physiological cyclic stretch and flow conditions and used to generate a blood-brain barrier model were exposed to 20 nm PEGylated AuNPs. An evaluation of toxic effects, cell stress, the release profile of pro-inflammatory cytokines, and blood-brain barrier properties showed that even under physiological conditions no obvious effects of PEGylated AuNPs on ECs were observed. These findings suggest that 20 nm-sized, PEGylated AuNPs may be a useful tool for biomedical applications, as they do not affect the normal function of healthy ECs after entering the blood stream.

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Section: Introductionmentioning

confidence: 99%

Gold nanoparticle interactions with endothelial cells cultured under physiological conditions

et al. 2017

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“…26,27 EC phenotypes vary between different organs, as well as between different tissues within the same organ. In addition, the gene expression profile of ECs can be significantly influenced by the tumor.…”

Section: Introductionmentioning

confidence: 99%

Design of universal cancer vaccines using natural tumor vessel-specific antigens (SANTAVAC)

Lokhov¹,

Balashova²

2015

Human Vaccines & Immunotherapeutics

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“…Local microenvironment is a major participating factor in establishment of endothelial cell heterogeneity, to an extent that when they are removed from their native environment and grown in culture, endothelial cells undergo phenotypic drift and lose many of their organ-specific characteristics (22)(23)(24). Analyses of the activation pattern of endothelial specific promoters in vitro and in vivo also reflect the heterogeneity of endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Sequences in Intron 51 of the von Willebrand Factor Gene Target Promoter Activation to a Subset of Lung Endothelial Cells in Transgenic Mice

Kleinschmidt

Nassiri

Stitt

et al. 2008

Journal of Biological Chemistry

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In vivo analyses of the VWF promoter previously demonstrated that a fragment spanning sequences ؊487 to ؉247 targets promoter activation to brain vascular endothelial cells, whereas a longer fragment including 2182 bp of the 5-flanking sequences, the first exon, and the first intron activated expression in endothelial cells of the heart and muscles as well as the brain of transgenic mice. These results suggested that additional VWF gene sequences were required for expression in other vascular endothelial cells in vivo. We have now identified a region within intron 51 of the VWF gene that is DNase I-hypersensitive (HSS) specifically in nonendothelial cells and interacts with endothelial and nonendothelial specific complexes that contain YY1. We demonstrate that ␤-actin is associated with YY1 specifically in the nucleus of nonendothelial cells and is a component of the nuclear protein complexes that interact with the DNase I-hypersensitive region. In vitro transfection analyses demonstrated that HSS sequences containing this YY1-binding site do not significantly affect VWF promoter activity. However, in vivo analyses demonstrated that addition of these sequences to the VWF promoter (؊487 to ؉247) results in promoter activation in lung and brain vascular endothelial cells. These results demonstrate that the HSS sequences in intron 51 of the VWF gene contain cis-acting elements that are necessary for the VWF gene transcription in a subset of lung endothelial cells in vivo.

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Phenotypic Heterogeneity of the Endothelium

Cited by 1,486 publications

References 182 publications

Gold nanoparticle interactions with endothelial cells cultured under physiological conditions

Gold nanoparticle interactions with endothelial cells cultured under physiological conditions

Design of universal cancer vaccines using natural tumor vessel-specific antigens (SANTAVAC)

Sequences in Intron 51 of the von Willebrand Factor Gene Target Promoter Activation to a Subset of Lung Endothelial Cells in Transgenic Mice

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