ArticleScientific reports2017
Restenosis Inhibition and Re-differentiation of TGFβ/Smad3-activated Smooth Muscle Cells by Resveratrol.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Resveratrol as an Anti-inflammatory Agent in Coronary Artery Disease: A Systematic Review, Meta-Analysis and Meta-Regression.Chinese journal of integrative medicine · 2024Pooled it
- Pharmacological and toxicological roles of Kruppel-like factors (KLFs) in the cardiovascular system: a review.Molecular biology reports · 2025Review
- Molecular landscape of atherosclerotic plaque progression: insights from proteomics, single-cell transcriptomics and genomics.BMC medicine · 2025Article
- Nano-based perivascular intervention sustains a nine-month long-term suppression of intimal hyperplasia in vein grafts.Bioactive materials · 2025Article
- The Role of TGF-β Signaling in Saphenous Vein Graft Failure after Peripheral Arterial Disease Bypass Surgery.International journal of molecular sciences · 2023Review
- Noncoding RNAs in Vascular Cell Biology and Restenosis.Biology · 2022Review
- Progress of Research into Novel Drugs and Potential Drug Targets against Porcine Pseudorabies Virus.Viruses · 2022Review
- Current knowledge of Krüppel-like factor 5 and vascular remodeling: providing insights for therapeutic strategies.Journal of molecular cell biology · 2021Review
- Targeting the epigenome in in-stent restenosis: from mechanisms to therapy.Molecular therapy. Nucleic acids · 2021Review
- Article
- Review
- Salusin-β Promotes Vascular CalcificationAntioxidants & redox signaling · 2019Article
- Hyperinsulinemia-induced KLF5 mediates endothelial angiogenic dysfunction in diabetic endothelial cells.Journal of molecular histology · 2019Article
- Resveratrol and Vascular Function.International journal of molecular sciences · 2019Review
- Therapeutic Effects of Resveratrol Liposome on Muscle Injury in Rats.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Analysis of Combined Transcriptomes Identifies Gene Modules that Differentially Respond to Pathogenic Stimulation of Vascular Smooth Muscle and Endothelial Cells.Scientific reports · 2018Article
- Krüppel-Like Factors in Vascular Inflammation: Mechanistic Insights and Therapeutic Potential.Frontiers in cardiovascular medicine · 2018Review
- Unimolecular Micelle-Based Hybrid System for Perivascular Drug Delivery Produces Long-Term Efficacy for Neointima Attenuation in Rats.Biomacromolecules · 2017Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
To date, there is no periadventitial drug delivery method available in the clinic to prevent restenotic failure of open vascular reconstructions. Resveratrol is a promising anti-restenotic natural drug but subject to low bioavailability when systemically administered. In order to reconcile these two prominent issues, we tested effects of periadventitial delivery of resveratrol on all three major pro-restenotic pathologies including intimal hyperplasia (IH), endothelium impairment, and vessel shrinkage. In a rat carotid injury model, periadventitial delivery of resveratrol either via Pluronic gel (2-week), or polymer sheath (3-month), effectively reduced IH without causing endothelium impairment and vessel shrinkage. In an in vitro model, primary smooth muscle cells (SMCs) were stimulated with elevated transforming growth factor (TGFβ) and its signaling protein Smad3, known contributors to IH. TGFβ/Smad3 up-regulated Kruppel-like factor (KLF5) protein, and SMC de-differentiation which was reversed by KLF5 siRNA. Furthermore, TGFβ/Smad3-stimulated KLF5 production and SMC de-differentiation were blocked by resveratrol via its inhibition of the Akt-mTOR pathway. Concordantly, resveratrol attenuated Akt phosphorylation in injured arteries. Taken together, periadventitial delivery of resveratrol produces durable inhibition of all three pro-restenotic pathologies - a rare feat among existing anti-restenotic methods. Our study suggests a potential anti-restenotic modality of resveratrol application suitable for open surgery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.