Cyclic strain amplitude dictates the growth response of vascular smooth muscle cells in vitro: role in in-stent restenosis and inhibition with a sirolimus drug-eluting stent

2012 ◽  
Vol 12 (4) ◽  
pp. 671-683 ◽  
Author(s):  
Alberto Colombo ◽  
Shaunta Guha ◽  
Joseph N. Mackle ◽  
Paul A. Cahill ◽  
Caitríona Lally
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle Cells ◽  
Growth Response ◽  
Cyclic Strain ◽  
Drug Eluting Stent ◽  
Stent Restenosis ◽  
Drug Eluting ◽  
Cyclic Strain Amplitude ◽  
In Stent Restenosis

scholarly journals A novel mechanism of Euonymine inhibits in-stent restenosis through enhancing contractile phenotype of VSMCs by targeting AKT1 and p38MAPK

2021 ◽  
Author(s):  
Li Zhang ◽  
Yi Ting Tao ◽  
Qin Hu ◽  
Ren Hua Yang ◽  
Jia Jia ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Contractile Phenotype ◽  
Stent Restenosis ◽  
Drug Eluting ◽  
In Stent Restenosis

This study aimed to examine the inhibitory effects of Euonymine on in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) and oxidized low-density lipoprotein (ox-LDL)-induced proliferation, migration, and pro-apoptotic of vascular smooth muscle cells (VSMCs) in vitro, and its potential mechanisms. Euonymine is a monomer component extracted from Tripterygium hypoglaucum (Levl) Hutch. Using in vitro models of rabbit carotid balloon injury and porcine atherosclerotic coronary implantation, we confirmed that Euonymine inhibited ISR after PCI. Furthermore, Euonymine inhibited VSMC phenotypic transformation by targeting AKT1 to regulate the PTEN/AKT1/m TOR signaling pathway, with exertion of anti-proliferative, anti-migratory, and pro-apoptotic effects on ox-LDL-induced cell injury model. Additionally, the study demonstrated that Euonymine induced apoptosis of VSMCs via the p38MAPK-related mitochondria-dependent apoptotic pathway. Collectively, these findings indicated that Euonymine drug-eluting stents inhibited ISR after PCI by targeting AKT1 and p38MAPK to enhance the contractile phenotype of VSMCs to prevent intimal hyperplasia development. This provides insights into a potential therapeutic strategy involving the beneficial effect of Euonymine drug-eluting stent on ISR. Keywords: Euonymine; Neointimal hyperplasia; Vascular smooth muscle cells, PTEN/AKT1/mTOR;p38MAPK; Proliferation; Migration; Apoptosis.

scholarly journals An Engineered Gene Nanovehicle Developed for Smart Gene Therapy to Selectively Inhibit Smooth Muscle Cells: An In Vitro Study

2020 ◽  
Vol 21 (4) ◽  
pp. 1530
Author(s):  
Ling-Yi Cheng ◽  
Yu-Chi Wang ◽  
Ming-Hong Chen ◽  
Fu-I Tung ◽  
Kuan-Ming Chiu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Ex Vivo ◽  
Vascular Endothelial Cell ◽  
Balloon Catheter ◽  
In Vitro Study ◽  
Vitro Study ◽  
Stent Restenosis ◽  
Drug Eluting ◽  
In Stent Restenosis

In-stent restenosis is a serious concern for patients treated through the stenting procedure, although this can be solved using drug-eluting stents and/or drug-eluting balloon catheters. However, the chemical agents released from the drug-eluting layer for inhibiting smooth muscle cell (SMC) migration are inevitably associated with damage to vascular endothelial cell (ECs). The present in vitro study used a distinct strategy, in which a smart gene (phEGR1-PKCδ, an engineered plasmid consists of an SMC-specific promoter (human early growth response 1, hEGR1 promoter) ligated with a gene encoding apoptosis-inducing protein (protein kinase C-delta, PKCδ) was incorporated into a novel gene vehicle (Au cluster-incorporated polyethylenimine/carboxymethyl hexanoyl chitosan, PEI-Au/CHC) to form the PEI-Au/CHC/phEGR1-PKCδ complex, which was proposed for the selective inhibition of SMC proliferation. It was found that the cell viability of SMCs receiving the PEI-Au/CHC/phEGR1-PKCδ complex under simulated inflammation conditions was significantly lower than that of the ECs receiving the same treatment. In addition, the PEI-Au/CHC/phEGR1-PKCδ complex did not demonstrate an inhibitory effect on EC proliferation and migration under simulated inflammation conditions. Finally, the PEI-Au/CHC/phEGR1-PKCδ complexes coated onto a balloon catheter used in percutaneous transluminal coronary angioplasty (PTCA) could be transferred to both the ECs and the SMC layer of Sprague Dawley (SD) rat aortas ex vivo. These preliminary in vitro results suggest that the newly developed approach proposed in the present study might be a potential treatment for reducing the incidence rate of in-stent restenosis and late thrombosis in the future.

scholarly journals Drug-eluting stent specifically designed to target vascular smooth muscle cell phenotypic modulation attenuated restenosis through the YAP pathway

2019 ◽  
Vol 317 (3) ◽  
pp. H541-H551 ◽  
Author(s):  
Chen Huang ◽  
Wenwen Zhang ◽  
Yuelin Zhu
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Contractile Protein ◽  
Drug Eluting Stent ◽  
Phenotypic Modulation ◽  
Sorafenib Treatment ◽  
Stent Restenosis ◽  
Drug Eluting ◽  
In Stent Restenosis

Vascular smooth muscle cell (SMC) phenotypic modulation contributes to the development of restenosis. A sorafenib-eluting stent was specifically designed to target SMC phenotypic modulation to inhibit in-stent restenosis in the present study. SMC contractile protein from the freshly isolated rat aorta was expressed at a high level, but its expression was dramatically reduced after SMCs were cultured in 10% FBS for 1 wk. After sorafenib treatment, SMC contractile protein expression was markedly upregulated. We further observed that Yes-associated protein (YAP) expression was attenuated after sorafenib treatment in a dose-dependent manner. Overexpression of YAP by lentivirus reversed the expression of sorafenib-induced SMC contractile protein and increased the expression of cyclin D. Mechanistically, sorafenib regulated the serum response factor-myocardin (SRF-Myocd) complex through competitive binding of YAP to Myocd and increased SRF binding to CArG-containing regions of SMC-specific contractile genes within intact chromatin, thereby controlling the activity of smooth muscle-specific gene transcription. In a rabbit carotid model, the sorafenib-eluting stent (SFES) dramatically inhibited in-stent restenosis and upregulated SMC contractile protein expression. Overexpression of YAP blocked the antirestenosis effect of SFES and repressed contractile smooth muscle-specific genes in vivo, indicating that SFES attenuated in-stent restenosis through YAP-mediated SMC phenotypic modulation. We demonstrated that SFES attenuated in-stent restenosis through YAP-mediated SMC phenotypic modulation. Targeting SMC phenotypic modulation by drug-eluting stent represents an attractive therapeutic approach for the treatment of occlusive vascular diseases. NEW & NOTEWORTHY In the present study, we demonstrated that sorafenib regulates smooth muscle cell (SMC) phenotypic modulation from a proliferative to a contractile state. Sorafenib induced a myocardin-serum response factor interaction and increased SMC contractile gene transcription through the Yes-associated protein pathway. Moreover, local delivery of sorafenib regulating SMC phenotypic modulation represents a promising strategy in the design of drug-eluting stents.

scholarly journals TCTAP A-030 Drug Coated Balloon Versus Drug-eluting Stent for In-stent Restenosis After Drug-eluting Stent Implantation: A Meta-analysis

2021 ◽  
Vol 77 (14) ◽  
pp. S19
Author(s):  
Hendy Bhaskara Perdana Putra ◽  
Quri Meihaerani Savitri ◽  
Wally Wahyu Mukhammad ◽  
Atiyatum Billah ◽  
Alan Dharmasaputra ◽  
...  
Keyword(s):  
Stent Implantation ◽  
Meta Analysis ◽  
Drug Eluting Stent ◽  
Stent Restenosis ◽  
Drug Eluting ◽  
Drug Coated Balloon ◽  
In Stent Restenosis

The effect of REDV/TiO2 coating coronary stents on in-stent restenosis and re-endothelialization

2016 ◽  
Vol 31 (6) ◽  
pp. 911-922 ◽  
Author(s):  
Xiangshan Xu ◽  
Lijie Wang ◽  
Guofeng Wang ◽  
Yuanzhe Jin
Keyword(s):  
Metal Ion ◽  
316L Stainless Steel ◽  
Ceramic Coating ◽  
Bare Metal Stent ◽  
Drug Eluting Stent ◽  
Bare Metal ◽  
Metal Stent ◽  
Stent Restenosis ◽  
Drug Eluting ◽  
In Stent Restenosis

The coronary artery stent has been widely used in clinic. In-stent restenosis was mainly caused by the excessive proliferation of smooth muscle cell and the inflammation due to the metal ion released from stent scaffold of the drug-eluting stent. Thus, to reduce the in-stent restenosis and promote the vascular endothelialization have become a hot research point in this area. In this paper, a nano-TiO2 ceramic coating was deposited on 316L stainless steel to reduce the metal ion release and to inhibit the inflammation reaction. An endothelia cell selective adhesion peptide Arg-Glu-Asp-Val (REDV) coating was prepared on the ceramic coating by a polydopamine technology to promote the endothelialization. The corrosion test indicated that nano-TiO2 ceramic film could effectively decrease the nickel ion released from 316L stainless steel. REDV/TiO2 coating could promote the endothelial cell adhesion and proliferation, meanwhile REDV/TiO2 coating could also increase the nitric oxide concentration. Bare metal stent, TiO2-coated stent and REDV/TiO2-coated stent were implanted in the iliac arteries of rabbit model. In-stent restenosis and re-endothelialization were evaluated at 28 days post-implantation of the stents. The results showed that REDV/TiO2-coated stents could effectively reduce in-stent restenosis and promote re-endothelialization in comparison with TiO2-coated drug-eluting stent and bare metal stent. These results suggest that REDV/TiO2-coated drug-eluting stent maybe a good choice of the application for coronary artery disease.

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