Decoy oligodeoxynucleotide againstactivator protein-1 reducesneointimal proliferation after coronaryangioplasty in hypercholesterolemic minipigs

Buchwald, A.; Wagner, Andreas H.; Webel, Christian; Hecker, Markus

doi:10.1016/s0735-1097(01)01797-1

Cited by 39 publications

(33 citation statements)

References 16 publications

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“…Our data are consistent with the idea that activation of ERK, AP-1, and NF-B and downstream targets such as ET-1 and cyclin D1 contributes to cardiac remodeling following injury due to T. cruzi infection. The possibility of targeting components of the MAPK or the cell cycle pathways is now gaining acceptance as a therapeutic modality for cardiovascular disease, and the data in this paper suggest that this type of adjunctive therapy may be also useful in Chagas' disease (1,6,21,27,34,49). …”

Section: Discussionmentioning

confidence: 98%

“…The injury to the vessel results in smooth muscle cell proliferation, migration, and the production of extracellular matrix. Activation of ERK and AP-1 resulting in smooth muscle cell proliferation occurs as a result of balloon injury to the carotid and coronary arteries in animal models and has been reported to be reduced by the administration of PD98059, an inhibitor of the MAPK pathway (6,17,34,36). In addition, shortly following balloon angioplasty, there is a marked induction of cyclins and cyclin-dependent kinases (11,24,25,34,63).…”

Section: Discussionmentioning

confidence: 99%

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Activation of Transcription Factors AP-1 and NF-κB in Murine Chagasic Myocarditis

Huang¹,

Petkova²,

Cohen³

et al. 2003

Infect Immun

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Activation of Transcription Factors AP-1 and NF-κB in Murine Chagasic Myocarditis

Huang¹,

Petkova²,

Cohen³

et al. 2003

Infect Immun

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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. Thus, the presence of the −475C sequence in the CCNB1 promoter may enhance gene transcription through increased recruitment of AP-1 transcription factors.…”

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 effectiveness of this antiproliferative therapy has been demonstrated in experimental and major randomized clinical studies [1][2][3][4][5][6]. Late stent thrombosis, the "edge effect", and "geographic miss" initially proved to be clinical problems, but were resolved by long-term dual antiplatelet treatment, higher radiation doses, and overlapping radiation sources proximal and distal to the target lesion [7,8]. Despite the initial success of antiproliferative radiation therapy, the longer-term clinical results leave room for skepticism.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical and animal studies show that late thrombosis remains a clinical issue unless dual antiplatelet treatment is sustained for good. Neointimal proliferation is not substantially inhibited and late lumen loss with a "catch-up" proliferation can occur [7][8][9][10]. Implantation of drug eluting stents (DES) is the currently most promising therapy for the treatment of coronary artery disease and restenosis.…”

Section: Introductionmentioning

confidence: 99%

Nf-κb and AP-1 activation is associated with late lumen loss after porcine coronary angioplasty and antiproliferative beta-irradiation

Deiner

Shagdarsuren

Schwimmbeck

et al. 2007

Cardiovascular Research

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Objective: Despite the success of antiproliferative therapies, restenosis remains a common problem after percutaneous transluminal coronary angioplasty (PTCA). Longer-term clinical results of brachytherapy (intracoronary radiation), the lack of long-term clinical results after implantation of drug eluting stents, and the occurrence of late thrombosis after both procedures leave room for skepticism. Neointimal proliferation is not substantially inhibited at late time points after brachytherapy, and late lumen loss with a "catch-up" proliferation can occur. We hypothesized that the transcription factors nuclear factor-{kappa}B (NF-κB) and activator protein-1 (AP-1) are involved in these processes. We addressed the role of these mediators in a porcine model of coronary restenosis. Methods: Thirty-nine pigs underwent PTCA in two major coronary arteries. One of the two balloon-injured arteries was randomly assigned to receive immediate 20 Gy beta-irradiation (Brachy group) using a noncentered source train ( 90 Sr/Y Beta-Cath, Novoste). Animals were sacrificed after 1 day, 14 days, or 28 days. Proliferating cells were labeled prior to euthanasia. Results: At late time points, lumen area was significantly smaller and the inflammatory response was more pronounced in the Brachy group than in the PTCA group. These findings coincided with sustained activation of MMP-9 and transcription factors like NF-κB and AP-1. Initially, cell proliferation was reduced in the Brachy group; however, at late time points, differences between the two treatment groups were no longer significant. Conclusions: Brachytherapy initially inhibits cell proliferation; however, cellular and molecular inflammatory processes (e.g. activation of NF−κB) are enhanced within the arterial wall. This proinflammatory side effect may be responsible for the observed delayed proliferation and the resulting lumen loss.

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Decoy oligodeoxynucleotide againstactivator protein-1 reducesneointimal proliferation after coronaryangioplasty in hypercholesterolemic minipigs

Cited by 39 publications

References 16 publications

Activation of Transcription Factors AP-1 and NF-κB in Murine Chagasic Myocarditis

Activation of Transcription Factors AP-1 and NF-κB in Murine Chagasic Myocarditis

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

Nf-κb and AP-1 activation is associated with late lumen loss after porcine coronary angioplasty and antiproliferative beta-irradiation

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