The role of c-jun in PDTC-sensitive flow-dependent restenosis after angioplasty and stenting

Murrell, Melanie; Khachigian, Levon M.; Ward, Michael R.

doi:10.1016/j.atherosclerosis.2006.11.016

Cited by 11 publications

(8 citation statements)

References 18 publications

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“…Moreover, Dz13 inhibits SMC proliferation and migration potentiated by Adeno-c-Jun. Third, Dz13 inhibits intimal thickening in a rabbit end-to-side vein graft model and builds on our earlier demonstration of c-Jun DNAzyme suppression of neointima formation in rat (7) and rabbit (8) arteries. Finally, we demonstrate here that shearand injury-inducible Egr-1 expression is suppressed by the c-Jun DNAzyme.…”

Section: Discussionmentioning

confidence: 99%

“…Dz13 has previously been used in animal models of arterial injury (7,8), but it has not been deployed in models of autologous vein transplantation. Using the E2F decoy approach of intra-operative, ex vivo oligonucleotide delivery, we incubated rabbit jugular veins in a solution containing Dz13 or Dz13scr then grafting the vein into the carotid artery of the same animal end to side, as is performed in standard CABG.…”

Section: Volume 285 • Number 6 • February 5 2010mentioning

confidence: 99%

“…c-Jun is poorly expressed in uninjured arteries but activated by injury (7). Previous studies from our group have shown that catalytic oligodeoxynucleotides (DNAzymes) targeting c-Jun inhibit intimal thickening in carotid arteries following permanent ligation (7) and balloon injury (8). Here we evaluated the effect of targeted inhibition of c-Jun on intimal hyperplasia in human saphenous veins, and of vein graft stenosis after autologous end-to-side transplantation in rabbits.…”

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confidence: 99%

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c-Jun Regulates Shear- and Injury-inducible Egr-1 Expression, Vein Graft Stenosis after Autologous End-to-Side Transplantation in Rabbits, and Intimal Hyperplasia in Human Saphenous Veins

Waldman

Khachigian

2010

Journal of Biological Chemistry

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Coronary artery bypass graft failure represents an unsolved problem in interventional cardiology and heart surgery. Late occlusion of autologous saphenous vein bypass grafts is a consequence of neointima formation underpinned by smooth muscle cell (SMC) migration and proliferation. Poor long term patency and the lack of pharmacologic agents that prevent graft failure necessitate effective alternative therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Volume 285 • Number 6 • February 5 2010mentioning

confidence: 99%

mentioning

confidence: 99%

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c-Jun Regulates Shear- and Injury-inducible Egr-1 Expression, Vein Graft Stenosis after Autologous End-to-Side Transplantation in Rabbits, and Intimal Hyperplasia in Human Saphenous Veins

Waldman

Khachigian

2010

Journal of Biological Chemistry

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“…In the present study, sunitinib inhibited PDGF-induced ERK phosphorylation in vitro and in vivo . In addition, other downstream signaling molecules, including protein kinase B and c-Jun N-terminal kinase, may contribute to the inhibitory effect of sunitinib (25–27). These molecules differentially regulate SMC growth and migration via distinct signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

A novel PDGF receptor inhibitor-eluting stent attenuates in-stent neointima formation in a rabbit carotid model

Huang

Mei

Zhou

et al. 2016

Molecular Medicine Reports

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A novel drug-eluting stent (DES) is required to target vascular smooth muscle cells (SMCs) without harming endothelial cells (ECs). Platelet-derived growth factor (PDGF) is critical for the proliferation and migration of SMCs. Sunitinib [a PDGF receptor (PDGFR) tyrosine kinase inhibitor]-eluting stents may therefore inhibit neointimal formation. The aim of the present study was to examine the stent-based delivery of sunitinib in a rabbit carotid model; in addition, the effects of sunitinib were evaluated in vitro. Local administration of sunitinib markedly reduced neointimal formation without delaying re-endothelialization in the carotid artery model. In vitro, sunitinib inhibited SMC proliferation; however, no effects were observed on ECs. Sunitinib caused necrosis of SMCs. In addition, sunitinib attenuated PDGF-stimulated SMC migration in a scratch wound assay and inhibited α-SMA cytoskeleton polymerization. Furthermore, sunitinib inhibited PDGF-induced phosphorylation of extracellular signal-regulated kinase in vitro and in vivo. Therefore, this novel DES may be a potential strategy for the treatment of vascular disorders.

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“…35 AP-1 is induced after balloon angioplasty [36][37][38] and stenting, 39 and gene therapy against AP-1 reduces neointima development in animal models. 36,40,41 Our data show that the restenosis-risk C allele of −475[T/C] in the CCNB1 promoter binds AP-1 with affinity higher than that of the T variant, and that overexpression of the AP-1 family member c-Fos significantly augments luciferase activity driven by a tandem repeat of −475C, with no significant effect on a similar construct driven by −475T.…”

Section: In This Study We Show That the Snps Rs350099 (−957[t/c]) Rmentioning

confidence: 99%

Genetic Variants in CCNB1 Associated With Differential Gene Transcription and Risk of Coronary In-Stent Restenosis

Silvestre-Roig¹,

Fernández²,

Mansego³

et al. 2014

Circ Cardiovasc Genet

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Background-The development of diagnostic tools to assess restenosis risk after stent deployment may enable the intervention to be tailored to the individual patient, for example, by targeting the use of drug-eluting stent to highrisk patients, with the goal of improving safety and reducing costs. The CCNB1 gene (encoding cyclin B1) positively regulates cell proliferation, a key component of in-stent restenosis. Therefore, we hypothesized that single-nucleotide polymorphisms in CCNB1 may serve as useful tools in risk stratification for in-stent restenosis. The incidence of restenosis is highly influenced by clinical, biological, and procedural and lesion-related risk factors. 4 However, information on restenosis biomarkers is scarce. Single-nucleotide polymorphisms (SNPs) are recognized as suitable markers of disease predisposition. Methods and Results-We5 SNPs in the human genome occur on average once every 300 nucleotides (≈10 million SNPs), making them the most common type of genetic variation. SNPs reported to influence restenosis risk affect platelet activation, leukocyte recruitment, the inflammatory response, metalloproteinases, lipid metabolism, oxidative stress, nitric oxide, the renin-angiotensin system, and cell proliferation. 4,6,7 Interestingly, the 838C>A SNP in CDKN1B (encoding the tumor suppressor p27 Kip1 ) has been associated with restenosis risk after coronary stenting, which might be because of augmented vascular smooth muscle cell proliferation caused by reduced CDKN1B promoter activity in patients carrying the risk allele.8 However, other SNPs in CDKN1B or TP53 (encoding the tumor suppressor p53) showed lack of association with restenosis risk. 8,9 In the present study, we investigated a potential association of restenosis risk with SNPs in the CCNB1 gene (encoding cyclin B1). Cyclin B1 is essential for cell proliferation, and its ablation in the mouse is embryonically lethal.10 Several regulatory mechanisms are necessary to ensure that cyclin B1 protein accumulates appreciably only during the G2/M cell cycle transition, and deregulated CCNB1 transcription leading to aberrantly high levels of cyclin B1 throughout the cell cycle is associated with excessive hyperplasia in several human cancers.11 Several lines of evidence indicate that cyclin B1 is also important in the context of cardiovascular disease: its expression has been reported in human restenotic tissue obtained by directional coronary atherectomy, 12 it is induced in balloon-injured rat carotid artery, 13,14 and its inhibition reduces neointimal thickening in this animal model. 15 Herein, we present evidence from 2 independent cohorts of patients undergoing coronary stent deployment (Clinica Mediterranea and Genetic risk factors for In-Stent Hyperplasia study Amsterdam [GEISHA]) 8 cohorts showing that alleles of the SNPs rs350099, rs350104, and rs164390, located in regulatory regions of CCNB1, are associated with higher CCNB1 mRNA expression and increased risk of in-stent restenosis (ISR) after PCI. Furthermore, we identify mole...

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The role of c-jun in PDTC-sensitive flow-dependent restenosis after angioplasty and stenting

Cited by 11 publications

References 18 publications

c-Jun Regulates Shear- and Injury-inducible Egr-1 Expression, Vein Graft Stenosis after Autologous End-to-Side Transplantation in Rabbits, and Intimal Hyperplasia in Human Saphenous Veins

c-Jun Regulates Shear- and Injury-inducible Egr-1 Expression, Vein Graft Stenosis after Autologous End-to-Side Transplantation in Rabbits, and Intimal Hyperplasia in Human Saphenous Veins

A novel PDGF receptor inhibitor-eluting stent attenuates in-stent neointima formation in a rabbit carotid model

Genetic Variants in CCNB1 Associated With Differential Gene Transcription and Risk of Coronary In-Stent Restenosis

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