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Re-endothelialization of arteries assessed by scanning electron microscopy at 3 months post stent implantation.
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Background
Carotid artery stenosis is a major risk factor for ischemic stroke. Although carotid angioplasty and stenting using an embolic protection device has been introduced as a less invasive carotid revascularization approach, in-stent restenosis limits its long-term efficacy and safety. The objective of this study was to test the anti-restenos...
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Objective: Thirty percent of all acute ischemic strokes cause is the internal carotid artery stenosis or occlusion. The carotid artery stenting (CAS) was rarely performed in early time, was used more frequently with the development of angiographic method and materials. In this study, we aimed to evaluate the success rates, clinical outcomes and com...
Objective:
To compare peri-operative any symptomatic stroke after carotid angioplasty and stenting (CAS), based on the application or absence of a cerebral protection device.
Methods:
A systematic literature review using PubMed, Embase, and the Cochrane Central was done across an online data base from January 1995 to October 2016. Procedures whi...
Citations
... The porcine CCA is often preferred for the preclinical testing of vascular grafts due to its anatomical and physiological similarity to human small-diameter arteries ( García et al., 2011). Porcine CCAs are currently often used as an experimental model in vascular surgery, such as designing stents used in the treatment of CCA obstruction or stenosis and in acute ischemic stroke (Fong et al., 2017;Jiang et al., 2016;Nikoubashman et al., 2018;Stewart et al., 2017;Sun et al., 2019;Zhou et al., 2016). To date, porcine CCAs have been used for testing various types of bioengineered vascular grafts, such as polytetrafluoroethylene (PTFE) and electrospun poly--caprolactone nanofibers (PCL) ( Kritharis et al., 2012;Jaramillo et al., 2018;Mrowczynski et al., 2014;Tzchori et al., 2018). ...
Background:
Using animal models in experimental medicine requires mapping of their anatomical variability. Porcine common carotid arteries (CCA) are often preferred for the preclinical testing of vascular grafts due to their anatomical and physiological similarity to human small-diameter arteries. Comparing the microscopic structure of animal model organs to their human counterparts reveals the benefits and limitations of translational medicine.
Methods:
Using quantitative histology and stereology, we performed an extensive mapping of the regional proximodistal differences in the fractions of elastin, collagen, and smooth muscle actin as well as the intima-media and wall thicknesses among 404 segments (every 1 cm) of porcine CCAs collected from male and female pigs (n = 21). We also compared the microscopic structure of porcine CCAs with segments of human coronary arteries and one of the preferred arterial conduits used for the coronary artery bypass grafting (CABG), namely, the internal thoracic artery (ITA) (n = 21 human cadavers).
Results:
The results showed that the histological structure of left and right porcine CCA can be considered equivalent, provided that gross anatomical variations of the regular branching patterns are excluded. The proximal elastic carotid (51.2% elastin, 4.2% collagen, and 37.2% actin) transitioned to more muscular middle segments (23.5% elastin, 4.9% collagen, 54.3% actin) at the range of 2-3 centimeters and then to even more muscular distal segments (17.2% elastin, 4.9% collagen, 64.0% actin). The resulting morphometric data set shows the biological variability of the artery and is made available for biomechanical modeling and for performing a power analysis and calculating the minimum number of samples per group when planning further experiments with this widely used large animal model.
Conclusions:
Comparison of porcine carotids with human coronary arteries and ITA revealed the benefits and the limitations of using porcine CCAs as a valid model for testing bioengineered small-diameter CABG vascular conduits. Morphometry of human coronary arteries and ITA provided more realistic data for tailoring multilayered artificial vascular prostheses and the ranges of values within which the conduits should be tested in the future. Despite their limitations, porcine CCAs remain a widely used and well-characterized large animal model that is available for a variety of experiments in vascular surgery.
... First, although the most relevant translational effect of our study is the local delivery of Sema3A may serve as a potential treatment to prevent in-stent restenosis, the localized perivascular overexpression of Sema3A was inconsistent with the potential delivery approaches applied in patients. Recently, geneeluting stents (GES), such as viruses, plasmid DNA, siRNA and miRNA coated stents [47][48][49][50], are being researched in full swing. Further investigation using GES with viral-mediated gene transfer of Sema3A should be tested in a stent model to increase the translational potential of our current findings. ...
Background
Neointimal hyperplasia is a prominent pathological event during in-stent restenosis. Phenotype switching of vascular smooth muscle cells (VSMCs) from a differentiated/contractile to a dedifferentiated/synthetic phenotype, accompanied by migration and proliferation of VSMCs play an important role in neointimal hyperplasia. However, the molecular mechanisms underlying phenotype switching of VSMCs have yet to be fully understood.
Methods
The mouse carotid artery ligation model was established to evaluate Sema3A expression and its role during neointimal hyperplasia in vivo. Bioinformatics analysis, chromatin immunoprecipitation (ChIP) assays and promoter-luciferase reporter assays were used to examine regulatory mechanism of Sema3A expression. SiRNA transfection and lentivirus infection were performed to regulate Sema3A expression. EdU assays, Wound-healing scratch experiments and Transwell migration assays were used to assess VSMC proliferation and migration.
Findings
In this study, we found that semaphorin-3A (Sema3A) was significantly downregulated in VSMCs during neointimal hyperplasia after vascular injury in mice and in human atherosclerotic plaques. Meanwhile, Sema3A was transcriptionally downregulated by PDGF-BB via p53 in VSMCs. Furthermore, we found that overexpression of Sema3A inhibited VSMC proliferation and migration, as well as increasing differentiated gene expression. Mechanistically, Sema3A increased the NRP1-plexin-A1 complex and decreased the NRP1-PDGFRβ complex, thus inhibiting phosphorylation of PDGFRβ. Moreover, we found that overexpression of Sema3A suppressed neointimal hyperplasia after vascular injury in vivo.
Interpretation
These results suggest that local delivery of Sema3A may act as a novel therapeutic option to prevent in-stent restenosis.
Cardiovascular and cerebrovascular ischemic diseases seriously affect human health. Endovascular stent placement is an effective treatment but always leads to in-stent restenosis (ISR). Gene-eluting stent, which combines gene therapy with stent implantation, is a potential method to prevent ISR. In this study, an efficient gene-eluting stent was designed based on one new nucleic acid delivery system to decrease the possibility of ISR. The reduction-responsive branched nucleic acid vector (SKP) with low cytotoxicity was first synthesized via ring-opening reaction. The impressive in vitro transfection performances of SKP were proved using luciferase reporter, enhanced green fluorescent protein plasmid, and vascular endothelial growth factor plasmid (pVEGF). Subsequently, SKP/pVEGF complexes were coated on the surfaces of pre-treated clinical stents to construct gene-eluting stents (S-SKP/pVEGF). Anti-restenosis performance of S-SKP/pVEGF was evaluated via implanting stents into rabbit aortas. S-SKP/pVEGF could lead to the localized upregulation of VEGF proteins, improve the progress of re-endothelialization, and inhibit the development of ISR in vivo. Such efficient pVEGF-eluting stent with responsive nucleic acid delivery systems is very promising to prevent in-stent restenosis of cerebrovascular diseases.
Aim:
This article concisely recapitulates the different existing modes of stent mediated gene/drug delivery, their considerable advancements in clinical trials and a rationale of other merging new technologies such as nanotechnology and microRNA based therapeutics, furthermore addressing the breach in each of these perpetual stent platforms.
Discussion:
Over the past decade stent mediated gene/drug delivery have materialized as a hopeful alternative for cardiovascular disease and cancer in contrast to the routine conventional treatment modalities. Regardless of the phenomenal recent developments figured out with coronary interventions and cancer therapy by use of gene and drug eluting stents, practical hurdles still remain a challenge. The article moreover, highlights the limitations that each of the existing stent based gene/drug delivery system encompasses and therefore a vision for the future of discovering an ideal stent therapeutic platform that would circumvent all the practical hurdles witnessed with the existing technology.
Conclusion:
Further delve into improvisation of next generation DES to an extent has helped in overcoming the issue of restenosis. However, current stent formulations fall short of anticipated clinically meaningful outcomes and there is an explicit need for more randomized trials to further evaluate stent platforms in favour of enhanced safety and clinical value. GES may hold promise in contributing new ideas for stent based prevention of in-stent restenosis through genetic interventions by capitalizing wide variety of molecular targets. Therefore, the heart of the matter directs us to foresee in finding an ideal stent therapeutic platform that would tackle all gaps in the existing technology.
