Rapid Development of Vein Graft Atheroma in ApoE-Deficient Mice

It is widely accepted that T cells play an important role in the destruction of beta cells leading to autoimmune type I diabetes, but the involved effector mechanisms have remained unclear. We addressed this issue by testing the role of perforin-dependent cytotoxicity in a disease model involving transgenic mice expressing glycoprotein of lymphocytic choriomeningitis virus (LCMV-GP) in the beta cells of the endocrine pancreas. In such mice, LCMV infection leads to a potent LCMV-GP-specific T cell response resulting in rapid development of diabetes. We report here that in perforin-deficient LCMV-GP transgenic mice, LCMV infection failed to induce diabetes despite the activation of LCMV-GP-specific T cells. Deletion of nu beta 6+ T cells in Mls-1a perforin-deficient mice and the activation of LCMV-GP-specific T cells in perforin-deficient LCMV-GP transgenic mice, however, indicated that thymic tolerance induction by negative selection was not affected by the disruption of the perforin gene and that there is no fundamental difference between the T cell repertoires of normal control and perforin-deficient mice. In addition, adoptive transfer of LCMV-GP-specific TCR transgenic perforin-deficient T cells activated by LCMV-GP recombinant vaccinia virus led to marked insulitis with infiltration of CD4+ and CD8+ T cells without the development of diabetes. These findings indicate that perforin-dependent cytotoxicity is not required for the initiation of insulitis but is crucial for the destruction of beta cells in the later phase of the disease process. Other mechanisms or soluble factors present in the inflammatory islet infiltrate apparently lack the ability to efficiently induce diabetogenic beta cell damage.

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Identification of potential crucial genes and pathways associated with vein graft restenosis based on gene expression analysis in experimental rabbits

PeerJ ◽

10.7717/peerj.4704 ◽

2018 ◽

Vol 6 ◽

pp. e4704 ◽

Cited By ~ 1

Author(s):

Qiang Liu ◽

Xiujie Yin ◽

Mingzhu Li ◽

Li Wan ◽

Liqiao Liu ◽

...

Keyword(s):

Gene Expression ◽

High Throughput ◽

Vein Graft ◽

Molecular Mechanisms ◽

Rapid Development ◽

Bypass Graft ◽

Functional Enrichment ◽

Ppi Network ◽

Hub Genes ◽

Network Analyses

Occlusive artery disease (CAD) is the leading cause of death worldwide. Bypass graft surgery remains the most prevalently performed treatment for occlusive arterial disease, and veins are the most frequently used conduits for surgical revascularization. However, the clinical efficacy of bypass graft surgery is highly affected by the long-term potency rates of vein grafts, and no optimal treatments are available for the prevention of vein graft restenosis (VGR) at present. Hence, there is an urgent need to improve our understanding of the molecular mechanisms involved in mediating VGR. The past decade has seen the rapid development of genomic technologies, such as genome sequencing and microarray technologies, which will provide novel insights into potential molecular mechanisms involved in the VGR program. Ironically, high throughput data associated with VGR are extremely scarce. The main goal of the current study was to explore potential crucial genes and pathways associated with VGR and to provide valid biological information for further investigation of VGR. A comprehensive bioinformatics analysis was performed using high throughput gene expression data. Differentially expressed genes (DEGs) were identified using the R and Bioconductor packages. After functional enrichment analysis of the DEGs, protein–protein interaction (PPI) network and sub-PPI network analyses were performed. Finally, nine potential hub genes and fourteen pathways were identified. These hub genes may interact with each other and regulate the VGR program by modulating the cell cycle pathway. Future studies focusing on revealing the specific cellular and molecular mechanisms of these key genes and pathways involved in regulating the VGR program may provide novel therapeutic targets for VGR inhibition.

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Topical HDL administration reduces vein graft atherosclerosis in apo E deficient mice

Atherosclerosis ◽

10.1016/j.atherosclerosis.2010.09.024 ◽

2011 ◽

Vol 214 (2) ◽

pp. 271-278 ◽

Cited By ~ 20

Author(s):

Yingmei Feng ◽

Stephanie C. Gordts ◽

Feng Chen ◽

Yanhua Hu ◽

Eline Van Craeyveld ◽

...

Keyword(s):

Vein Graft ◽

Apo E ◽

Deficient Mice

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Loss of poly(ADP-ribose) polymerase-2 leads to rapid development of spontaneous T-cell lymphomas in p53-deficient mice

Oncogene ◽

10.1038/onc.2010.11 ◽

2010 ◽

Vol 29 (19) ◽

pp. 2877-2883 ◽

Cited By ~ 34

Author(s):

L Nicolás ◽

C Martínez ◽

C Baró ◽

M Rodríguez ◽

A Baroja-Mazo ◽

...

Keyword(s):

T Cell ◽

Rapid Development ◽

T Cell Lymphomas ◽

Deficient Mice

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Circulating Progenitor Cells Regenerate Endothelium of Vein Graft Atherosclerosis, Which Is Diminished in ApoE-Deficient Mice

Circulation Research ◽

10.1161/01.res.0000097864.24725.60 ◽

2003 ◽

Vol 93 (8) ◽

Cited By ~ 134

Author(s):

Qingbo Xu ◽

Zhongyi Zhang ◽

Fergus Davison ◽

Yanhua Hu

Keyword(s):

Progenitor Cells ◽

Vein Graft ◽

Deficient Mice

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Reduced junctional Na+/Ca2+-exchanger activity contributes to sarcoplasmic reticulum Ca2+ leak in junctophilin-2-deficient mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00413.2014 ◽

2014 ◽

Vol 307 (9) ◽

pp. H1317-H1326 ◽

Cited By ~ 19

Author(s):

Wei Wang ◽

Andrew P. Landstrom ◽

Qiongling Wang ◽

Michelle L. Munro ◽

David Beavers ◽

...

Keyword(s):

Heart Failure ◽

Sarcoplasmic Reticulum ◽

Single Channel ◽

Rapid Development ◽

Mouse Heart ◽

Cellular Mechanisms ◽

Open Probability ◽

Deficient Mice

Expression silencing of junctophilin-2 (JPH2) in mouse heart leads to ryanodine receptor type 2 (RyR2)-mediated sarcoplasmic reticulum (SR) Ca2+ leak and rapid development of heart failure. The mechanism and physiological significance of JPH2 in regulating RyR2-mediated SR Ca2+ leak remains elusive. We sought to elucidate the role of JPH2 in regulating RyR2-mediated SR Ca2+ release in the setting of cardiac failure. Cardiac myocytes isolated from tamoxifen-inducible conditional knockdown mice of JPH2 (MCM-shJPH2) were subjected to confocal Ca2+ imaging. MCM-shJPH2 cardiomyocytes exhibited an increased spark frequency width with altered spark morphology, which caused increased SR Ca2+ leakage. Single channel studies identified an increased RyR2 open probability in MCM-shJPH2 mice. The increase in spark frequency and width was observed only in MCM-shJPH2 and not found in mice with increased RyR2 open probability with native JPH2 expression. Na+/Ca2+-exchanger (NCX) activity was reduced by 50% in MCM-shJPH2 with no detectable change in NCX expression. Additionally, 50% inhibition of NCX through Cd2+ administration alone was sufficient to increase spark width in myocytes obtained from wild-type mice. Additionally, superresolution analysis of RyR2 and NCX colocalization showed a reduced overlap between RyR2 and NCX in MCM-shJPH2 mice. In conclusion, decreased JPH2 expression causes increased SR Ca2+ leakage by directly increasing open probability of RyR2 and by indirectly reducing junctional NCX activity through increased dyadic cleft Ca2+. This demonstrates two novel and independent cellular mechanisms by which JPH2 regulates RyR2-mediated SR Ca2+ leak and heart failure development.

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Rapid development of colitis in NSAID-treated IL-10–deficient mice

Gastroenterology ◽

10.1053/gast.2002.1231527 ◽

2002 ◽

Vol 123 (5) ◽

pp. 1527-1542 ◽

Cited By ~ 194

Author(s):

Daniel J. Berg ◽

Juan Zhang ◽

Joel V. Weinstock ◽

Hanan F. Ismail ◽

Keith A. Earle ◽

...

Keyword(s):

Rapid Development ◽

Deficient Mice

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A New Synthetic FGF Receptor Antagonist Inhibits Arteriosclerosis in a Mouse Vein Graft Model and Atherosclerosis in Apolipoprotein E-Deficient Mice

PLoS ONE ◽

10.1371/journal.pone.0080027 ◽

2013 ◽

Vol 8 (11) ◽

pp. e80027 ◽

Cited By ~ 5

Author(s):

Frédérique Dol-Gleizes ◽

Nathalie Delesque-Touchard ◽

Anne-Marie Marès ◽

Anne-Laure Nestor ◽

Paul Schaeffer ◽

...

Keyword(s):

Apolipoprotein E ◽

Receptor Antagonist ◽

Vein Graft ◽

Fgf Receptor ◽

Deficient Mice

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Comparison of localization of metallothionein in tissues of metallothionein-deficient mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141585 ◽

1995 ◽

Vol 53 ◽

pp. 1042-1043

Author(s):

H. Nishimura ◽

R Nishimura ◽

D.L. Adelson ◽

A.E. Michaelska ◽

K.H.A. Choo ◽

...

Keyword(s):

Metal Binding ◽

Immunohistochemical Staining ◽

Squamous Epithelium ◽

Rabbit Antiserum ◽

Slight Modification ◽

Positive Control ◽

Heavy Metal Binding ◽

Critical Organ ◽

Metal Binding Protein ◽

Deficient Mice

Metallothionein (MT), a cysteine-rich heavy metal binding protein, has several isoforms designated from I to IV. Its major isoforms, I and II, can be induced by heavy metals like cadmium (Cd) and, are present in various organs of man and animals. Rodent testes are a critical organ to Cd and it is still a controversial matter whether MT exists in the testis although it is clear that MT is not induced by Cd in this tissue. MT-IV mRNA was found to localize within tongue squamous epithelium. Whether MT-III is present mainly glial cells or neurons has become a debatable topic. In the present study, we have utilized MT-I and II gene targeted mice and compared MT localization in various tissues from both MT-deficient mice and C57Black/6J mice (C57BL) which were used as an MT-positive control. For MT immunostaining, we have used rabbit antiserum against rat MT-I known to cross-react with mammalian MT-I and II and human MT-III. Immunohistochemical staining was conducted by the method described in the previous paper with a slight modification after the tissues were fixed in HistoChoice and embedded in paraffin.

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