Electrical stimulation inhibits neointimal hyperplasia after abdominal aorta balloon injury through the PTEN/p27Kip1 pathway

Zhang, Ping; Liu, Zhitao; He, Guangbin; Liu, Jianping; Feng, Jian

doi:10.1093/abbs/gmq089

Cited by 9 publications

(12 citation statements)

References 29 publications

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“…More likely, the difference in restenosis may be explained by induction of the cyclin-dependent kinase inhibitor p27 Kip1 . Stents loaded with 300 μg 6-MP showed increased p27 Kip1 expression in intimal SMC, in accordance with previous studies showing the relation between p27 Kip1 and neointima hyperplasia [ 32 , 33 ], and between p27 Kip1 and 6-MP or Nur77 [ 15 – 17 ].…”

Section: Discussionsupporting

confidence: 91%

Stents Eluting 6-Mercaptopurine Reduce Neointima Formation and Inflammation while Enhancing Strut Coverage in Rabbits

Ruiter

Tiel

Doornbos³

et al. 2015

PLoS ONE

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BackgroundThe introduction of drug-eluting stents (DES) has dramatically reduced restenosis rates compared with bare metal stents, but in-stent thrombosis remains a safety concern, necessitating prolonged dual anti-platelet therapy. The drug 6-Mercaptopurine (6-MP) has been shown to have beneficial effects in a cell-specific fashion on smooth muscle cells (SMC), endothelial cells and macrophages. We generated and analyzed a novel bioresorbable polymer coated DES, releasing 6-MP into the vessel wall, to reduce restenosis by inhibiting SMC proliferation and decreasing inflammation, without negatively affecting endothelialization of the stent surface.MethodsStents spray-coated with a bioresorbable polymer containing 0, 30 or 300 μg 6-MP were implanted in the iliac arteries of 17 male New Zealand White rabbits. Animals were euthanized for stent harvest 1 week after implantation for evaluation of cellular stent coverage and after 4 weeks for morphometric analyses of the lesions.ResultsFour weeks after implantation, the high dose of 6-MP attenuated restenosis with 16% compared to controls. Reduced neointima formation could at least partly be explained by an almost 2-fold induction of the cell cycle inhibiting kinase p27Kip1. Additionally, inflammation score, the quantification of RAM11-positive cells in the vessel wall, was significantly reduced in the high dose group with 23% compared to the control group. Evaluation with scanning electron microscopy showed 6-MP did not inhibit strut coverage 1 week after implantation.ConclusionWe demonstrate that novel stents coated with a bioresorbable polymer coating eluting 6-MP inhibit restenosis and attenuate inflammation, while stimulating endothelial coverage. The 6-MP-eluting stents demonstrate that inhibition of restenosis without leaving uncovered metal is feasible, bringing stents without risk of late thrombosis one step closer to the patient.

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Section: Discussionsupporting

confidence: 91%

Stents Eluting 6-Mercaptopurine Reduce Neointima Formation and Inflammation while Enhancing Strut Coverage in Rabbits

Ruiter

Tiel

Doornbos³

et al. 2015

PLoS ONE

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“…There are reports demonstrating that ES on a range of cell types reduced cell proliferation (Hernandez‐Bule et al, ; Oshima et al, , ; Sebastian et al, ; Thrivikraman et al, ; Wang et al, ; Zhang et al, ). Several mechanisms initiated by ES which inhibit cell proliferation include cell cycle arrest, intracellular Ca 2+ influx and upregulation of tumor suppressor proteins.…”

Section: The Effects Of Es On Cell Proliferationmentioning

confidence: 99%

“…Despite reports on the effects of ES inducing either increased or decreased cell apoptosis, several studies showed that ES resulted in no effect on cell apoptosis (Huang et al, ; Linkov et al, ; Pedrotty et al, ; Qi et al, ; Sebastian et al, ; Thrivikraman, Madras, & Basu, ; Zhang et al, ). These reports are summarized in Table .…”

Section: The Effects Of Es On Cell Apoptosismentioning

confidence: 99%

“…Five of these studies used Direct current square waves (DC) to stimulate the cells. Of these five studies, four used high voltage DC (100 mV/mm) to stimulate keratinocytes (Sebastian et al, ), Schwann cells (Huang et al, ) and olfactory ensheathing cells (Qi et al, ), and 300–400 mV/mm was used on vascular smooth muscle cells (Zhang et al, ), all of which had no effect on apoptosis. This is contradictory to other studies which showed increased apoptosis was induced by the application of high‐voltage ES nsPEF at 60 kV/mm to squamous cell carcinoma and hepatocellular carcinoma (Chen et al, ; Oshima et al, ; Wang et al, ).…”

Section: The Effects Of Es On Cell Apoptosismentioning

confidence: 99%

“…Bipolar electrical stimulation has also been used in the treatment of human carpal tunnel syndrome, and has been shown to improve the rate of sensory and motor nerve regeneration with Brain‐Derived Neurotrophic Factor (BDNF) signaling (Gordon, Amirjani, Edwards, & Chan, ). However, there is still a huge potential for the use of ES in treatment of conditions such as cancer (Chen et al, ; Matsuki et al, ), keloid disease (Sebastian, Allan, Allan, Colthurst, & Bayat, ), treatment of long standing nerve defects (Qi et al, ), skeletal muscle atrophy (Guo, Cheung, Yeung, Zhang, & Yeung, ) and many others (Griffin et al, ; Li, Zhang, Qiao, Wang, & Zhang, ; Zhang, Liu, He, Liu, & Feng, ).…”

Section: Introductionmentioning

confidence: 99%

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Effects of electrical stimulation on cell proliferation and apoptosis

Love

Palee

Chattipakorn

2017

Journal Cellular Physiology

124

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The application of exogenous electrical stimulation (ES) to cells in order to manipulate cell apoptosis and proliferation has been widely investigated as a possible method of treatment in a number of diseases. Alteration of the transmembrane potential of cells via ES can affect various intracellular signaling pathways which are involved in the regulation of cellular function. Controversially, several types of ES have proved to be effective in both inhibiting or inducing apoptosis, as well as increasing proliferation. However, the mechanisms through which ES achieves this remain fairly unclear. The aim of this review was to comprehensively summarize current findings from in vitro and in vivo studies on the effects of different types of ES on cell apoptosis and proliferation, highlighting the possible mechanisms through which ES induced these effects and define the optimum parameters at which ES can be used. Through this we hope to provide a greater insight into how future studies can most effectively use ES at the clinical trial stage.

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Recycled algae-based carbon materials as electroconductive 3D printed skeletal muscle tissue engineering scaffolds

Bilge

Ergene

Ebru

et al. 2021

J Mater Sci: Mater Med

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Skeletal muscle is an electrically and mechanically active tissue that contains highly oriented, densely packed myofibrils. The tissue has self-regeneration capacity upon injury, which is limited in the cases of volumetric muscle loss. Several regenerative therapies have been developed in order to enhance this capacity, as well as to structurally and mechanically support the defect site during regeneration. Among them, biomimetic approaches that recapitulate the native microenvironment of the tissue in terms of parallel-aligned structure and biophysical signals were shown to be effective. In this study, we have developed 3D printed aligned and electrically active scaffolds in which the electrical conductivity was provided by carbonaceous material (CM) derived from algae-based biomass. The synthesis of this conductive and functional CM consisted of eco-friendly synthesis procedure such as pre-carbonization and multi-walled carbon nanotube (MWCNT) catalysis. CM obtained from biomass via hydrothermal carbonization (CM-03) and its ash form (CM-03K) were doped within poly(ɛ-caprolactone) (PCL) matrix and 3D printed to form scaffolds with aligned fibers for structural biomimicry. Scaffolds were seeded with C2C12 mouse myoblasts and subjected to electrical stimulation during the in vitro culture. Enhanced myotube formation was observed in electroactive groups compared to their non-conductive counterparts and it was observed that myotube formation and myotube maturity were significantly increased for CM-03 group after electrical stimulation. The results have therefore showed that the CM obtained from macroalgae biomass is a promising novel source for the production of the electrically conductive scaffolds for skeletal muscle tissue engineering.

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Electrical stimulation inhibits neointimal hyperplasia after abdominal aorta balloon injury through the PTEN/p27Kip1 pathway

Cited by 9 publications

References 29 publications

Stents Eluting 6-Mercaptopurine Reduce Neointima Formation and Inflammation while Enhancing Strut Coverage in Rabbits

Stents Eluting 6-Mercaptopurine Reduce Neointima Formation and Inflammation while Enhancing Strut Coverage in Rabbits

Effects of electrical stimulation on cell proliferation and apoptosis

Recycled algae-based carbon materials as electroconductive 3D printed skeletal muscle tissue engineering scaffolds

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