Dataset Information

Drug-Eluting Stent Targeting Sp-1-Attenuated Restenosis by Engaging YAP-Mediated Vascular Smooth Muscle Cell Phenotypic Modulation.

ABSTRACT: Background Activation of the YAP (Yes-associated protein) pathway has been demonstrated to be related to smooth muscle cells (SMCs) phenotypic modulation and vessel restenosis. The aim of this study was to illustrate the molecular mechanisms that regulate the expression of YAP during the process of SMCs phenotypic switch. Whether the molecular basis identified in the study could be a potential therapeutic target for drug-eluting stents is further tested. Methods and Results In cell culture and in rat carotid arterial injury models, Sp-1 (specificity protein 1) expression was significantly induced, and correlated with SMCs proliferative phenotype. Overexpression of Sp-1 promoted SMCs proliferation and migration. Conversely, siSp-1 transfection or Sp-1 inhibitor Mithramycin A treatment attenuates SMC proliferation and migration. Through gain- and loss-function assays, we demonstrated that YAP was involved in Sp-1-mediated SMC phenotypic switch. Mechanistically, activated Sp-1 regulated YAP transcriptional expression through binding to its promoter. Moreover, we fabricated a Sp-1 inhibitor Mithramycin A-eluting stent and further tested it. In the rabbit carotid model, Mithramycin A-eluting stent inhibited YAP transcription and attenuated in-stent restenosis through regulating YAP-mediated SMC phenotypic switch. Conclusions Sp-1 controls phenotypic modulation of SMC by regulating transcription factor YAP. Drug-eluting stent targeting Sp-1 might represent a novel therapeutic strategy to prevent in-stent restenosis.

SUBMITTER: Huang C

PROVIDER: S-EPMC6988170 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Drug-Eluting Stent Targeting Sp-1-Attenuated Restenosis by Engaging YAP-Mediated Vascular Smooth Muscle Cell Phenotypic Modulation.

Huang Chen C Zhao Jie J Zhu Yuelin Y

Journal of the American Heart Association 20191227 1

Background Activation of the YAP (Yes-associated protein) pathway has been demonstrated to be related to smooth muscle cells (SMCs) phenotypic modulation and vessel restenosis. The aim of this study was to illustrate the molecular mechanisms that regulate the expression of YAP during the process of SMCs phenotypic switch. Whether the molecular basis identified in the study could be a potential therapeutic target for drug-eluting stents is further tested. Methods and Results In cell culture and i ...[more]

PMID: 31880978

Similar Datasets

Project description:Given the limited salvage options for in-stent restenosis (ISR) of drug-eluting stents (DES), our high-volume cardiac catheterization laboratory has been performing intracoronary brachytherapy (ICBT) in patients with recurrent ISR of DES. This study analyzes their baseline characteristics and assesses the safety/toxicity of ICBT in this high-risk population.A retrospective analysis of patients treated with ICBT between September 2012 and December 2014 was performed. Patients with ISR twice in a single location were eligible. Procedural complications included vessel dissection, perforation, tamponade, slow/absent blood flow, and vessel closure. Postprocedural events included myocardial infarction, coronary artery bypass graft, congestive heart failure, stroke, bleeding, thrombosis, embolism, dissection, dialysis, or death occurring within 72 hours. A control group of patients with 2 episodes of ISR at 1 location who underwent percutaneous coronary intervention without ICBT was identified. Unpaired t tests and χ2 tests were used to compare the groups.There were 134 (78%) patients in the ICBT group with 141 treated lesions and 37 (22%) patients in the control group. There was a high prevalence of hyperlipidemia (>95%), hypertension (>95%), and diabetes (>50%) in both groups. The groups were well-balanced with respect to age, sex, and pre-existing medical conditions, with the exception of previous coronary artery bypass graft being more common the ICBT group. Procedural complication rates were low in the control and ICBT groups (0% vs 4.5%, P = .190). Postprocedural event rates were low (<5%) in both groups. Readmission rate at 30 days was 3.7% in the ICBT group and 5.4% in the control group (P = .649).This is the largest recent known series looking at ICBT for recurrent ISR of DES. ICBT is a safe treatment option with similarly low rates (<5%) of procedural and postprocedural complications compared with percutaneous coronary intervention alone. This study establishes the safety of ICBT in a high-risk patient cohort.

Project description:BackgroundCurrently, drug-eluting balloon (DEB) appears to be an attractive alternative option for the treatment of in-stent restenosis (ISR). Nevertheless, the clinical outcomes of DEB have seldom been compared to those of new-generation drug-eluting stent (DES). Thus, this meta-analysis aimed to evaluate the safety and efficacy of DEB compared to those of new-generation DES in the treatment of ISR.MethodsA comprehensive search of electronic databases including PubMed, EMBASE, and Cochrane Library up to November 2, 2017 was performed to identify pertinent articles comparing DEB to new-generation DES for the treatment of ISR. In addition, conference proceedings for the scientific sessions of the American College of Cardiology, American Heart Association, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, and EuroPCR were also searched. The primary endpoint was target lesion revascularization (TLR) at the longest follow-up. Dichotomous variables were presented as risk ratios (RR s) with 95% confidence intervals (CI s), while the overall RR s were estimated using the Mantel-Haenszel random-effects model.ResultsFive randomized controlled trials (RCTs) and eight observational studies involving 2743 patients were included in the present meta-analysis. Overall, DEB was comparable to new-generation DES in terms of TLR (RR = 1.24, 95% CI: 0.89-1.72, P = 0.21), cardiac death (RR = 1.55, 95% CI: 0.89-2.71, P = 0.12), major adverse cardiovascular event (RR = 1.21, 95% CI: 0.98-1.48, P = 0.07), myocardial infarction (RR = 1.12, 95% CI: 0.72-1.76, P = 0.62), and stent thrombosis (RR = 0.95, 95% CI: 0.38-2.42, P = 0.92). However, DEB was associated with higher risk of all-cause mortality than new-generation DES (RR = 1.65, 95% CI: 1.09-2.50, P = 0.02). This was especially true in the real-world observational studies (RR = 1.79, 95% CI: 1.12-2.88, P = 0.02). In RCTs, however, no significant difference was found between the two treatment strategies in the risk of all-cause mortality.ConclusionsThe current meta-analysis showed that DEB and new-generation DES had comparable safety and efficacy for the treatment of ISR in RCTs. However, treatment with DEB was associated with higher risk of all-cause mortality in the real-world nonrandomized studies.

Dataset Information

Drug-Eluting Stent Targeting Sp-1-Attenuated Restenosis by Engaging YAP-Mediated Vascular Smooth Muscle Cell Phenotypic Modulation.

Publications

Drug-Eluting Stent Targeting Sp-1-Attenuated Restenosis by Engaging YAP-Mediated Vascular Smooth Muscle Cell Phenotypic Modulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets