Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation

Sato, Junya; Kinugasa, Mitsuo; Satomi‐Kobayashi, Seimi; Hatakeyama, Kinta; Knox, Aaron; Asada, Yujiro; Wierman, Margaret E.; Hirata, Ken‐ichi; Rikitake, Yoshiyuki

doi:10.1371/journal.pone.0107236

Cited by 20 publications

(16 citation statements)

References 22 publications

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“…Translocation of p65 of NFκB from cytoplasm to nucleus is recognized as a prerequisite for the transcription 25 . VCAM-1 and ACAT-1 expressions at sites of atherosclerotic lesion formation are majorly controlled by NFκB system in early atherosclerotic lesions 26 . We found that salusin-β induced p65-NFκB nuclear translocation and recruitment of p65 to promoters of ACAT-1 and VCAM-1 in VSMCs.…”

Section: Discussionmentioning

confidence: 99%

Salusin-β induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NFκB pathway

Sun

Zhao

Liu

et al. 2016

Sci Rep

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Vascular smooth muscle cells (VSMCs) are indispensible components in foam cell formation. Salusin-β is a stimulator in the progression of atherosclerosis. Here, we showed that salusin-β increased foam cell formation evidenced by accumulation of lipid droplets and intracellular cholesterol content, and promoted monocyte adhesion in human VSMCs. Salusin-β increased the expressions and activity of acyl coenzyme A:cholesterol acyltransferase-1 (ACAT-1) and vascular cell adhesion molecule-1 (VCAM-1) in VSMCs. Silencing of ACAT-1 abolished the salusin-β-induced lipid accumulation, and silencing of VCAM-1 prevented the salusin-β-induced monocyte adhesion in VSMCs. Salusin-β caused p65-NFκB nuclear translocation and increased p65 occupancy at the ACAT-1 and VCAM-1 promoter. Inhibition of NFκB with Bay 11-7082 prevented the salusin-β-induced ACAT-1 and VCAM-1 upregulation, foam cell formation and monocyte adhesion in VSMCs. Scavenging ROS, inhibiting NADPH oxidase or knockdown of NOX2 abolished the effects of salusin-β on ACAT-1 and VCAM-1 expressions, p65-NFκB nuclear translocation, lipid accumulation and monocyte adhesion in VSMCs. Salusin-β increased miR155 expression, and knockdown of miR155 prevented the effects of salusin-β on ACAT-1 and VCAM-1 expressions, p65-NFκB nuclear translocation, lipid accumulation, monocyte adhesion and ROS production in VSMCs. These results indicate that salusin-β induces foam formation and monocyte adhesion via miR155/NOX2/NFκB-mediated ACAT-1 and VCAM-1 expressions in VSMCs.

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Section: Discussionmentioning

confidence: 99%

Salusin-β induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NFκB pathway

Sun

Zhao

Liu

et al. 2016

Sci Rep

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“…62 BRINP3 expression is also implicated in the modulation of reactive oxygen species production and NF-kB activity with downstream effects on leukocyte adhesion and inflammation in humans. 64 Although the peak lies a considerable distance from BRINP3, it is relatively narrow and is supported by a large number of SNPs ( Figure 3A), possibly including cis-regulatory elements.…”

Section: Top Candidate Genesmentioning

confidence: 93%

Natural Selection on Genes Related to Cardiovascular Health in High-Altitude Adapted Andeans

Crawford

Amaru

Song

et al. 2017

The American Journal of Human Genetics

101

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The increase in red blood cell mass (polycythemia) due to the reduced oxygen availability (hypoxia) of residence at high altitude or other conditions is generally thought to be beneficial in terms of increasing tissue oxygen supply. However, the extreme polycythemia and accompanying increased mortality due to heart failure in chronic mountain sickness most likely reduces fitness. Tibetan highlanders have adapted to high altitude, possibly in part via the selection of genetic variants associated with reduced polycythemic response to hypoxia. In contrast, high-altitude-adapted Quechua- and Aymara-speaking inhabitants of the Andean Altiplano are not protected from high-altitude polycythemia in the same way, yet they exhibit other adaptive features for which the genetic underpinnings remain obscure. Here, we used whole-genome sequencing to scan high-altitude Andeans for signals of selection. The genes showing the strongest evidence of selection-including BRINP3, NOS2, and TBX5-are associated with cardiovascular development and function but are not in the response-to-hypoxia pathway. Using association mapping, we demonstrated that the haplotypes under selection are associated with phenotypic variations related to cardiovascular health. We hypothesize that selection in response to hypoxia in Andeans could have vascular effects and could serve to mitigate the deleterious effects of polycythemia rather than reduce polycythemia itself.

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“…However, the expression level of BRINP3 was low in iPSCs, therefore, we cannot exclude the possibility that this result was an artifact. Nevertheless, the Chr1-eGSH locus may not be a suitable locus for therapeutic gene integration, as BRINP3 could be associated with pituitary gonadotropinomas [43] and inflammation [44], Notably, CTCF ChIA-PET analysis predicted this distant interaction, which has not been previously reported [40]. Although we used a public ChIA-PET dataset which was not generated from hiPSCs, our results suggested that bioinformatics approaches could be powerful tools for exploring the ideal human GSH and predicting the effect of genome editing.…”

Section: Discussionmentioning

confidence: 99%

Human Genomic Safe Harbors and the Suicide Gene-Based Safeguard System for iPSC-Based Cell Therapy

Kimura

Shofuda

Higuchi

et al. 2019

Stem Cells Translational Medicine

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The use of human induced pluripotent stem cells (hiPSCs) and recent advances in cell engineering have opened new prospects for cell‐based therapy. However, there are concerns that must be addressed prior to their broad clinical applications and a major concern is tumorigenicity. Suicide gene approaches could eliminate wayward tumor‐initiating cells even after cell transplantation, but their efficacy remains controversial. Another concern is the safety of genome editing. Our knowledge of human genomic safe harbors (GSHs) is still insufficient, making it difficult to predict the influence of gene integration on nearby genes. Here, we showed the topological architecture of human GSH candidates, AAVS1 , CCR5 , human ROSA26 , and an extragenic GSH locus on chromosome 1 (Chr1‐eGSH). Chr1‐eGSH permitted robust transgene expression, but a 2 Mb‐distant gene within the same topologically associated domain showed aberrant expression. Although knockin iPSCs carrying the suicide gene, herpes simplex virus thymidine kinase ( HSV‐TK ), were sufficiently sensitive to ganciclovir in vitro, the resulting teratomas showed varying degrees of resistance to the drug in vivo. Our findings suggest that the Chr1‐eGSH is not suitable for therapeutic gene integration and highlight that topological analysis could facilitate exploration of human GSHs for regenerative medicine applications. Our data indicate that the HSV‐TK/ganciclovir suicide gene approach alone may be not an adequate safeguard against the risk of teratoma, and suggest that the combination of several distinct approaches could reduce the risks associated with cell therapy. stem cells translational medicine 2019;8:627&638

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Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation

Cited by 20 publications

References 22 publications

Salusin-β induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NFκB pathway

Salusin-β induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NFκB pathway

Natural Selection on Genes Related to Cardiovascular Health in High-Altitude Adapted Andeans

Human Genomic Safe Harbors and the Suicide Gene-Based Safeguard System for iPSC-Based Cell Therapy

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