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Journal ArticleDOI

Static and Flow Conditions: Endothelial Cell Migration onto Metal Stent Surfaces.

TL;DR: The influence of hemodynamics on endothelial cell migration, both in vivo and in vitro, is reviewed, and recent in vitro studies demonstrating the importance of the nature of metal substrates in modulating endothelium cell migration rate are presented.
Abstract: Restenosis associated with intimal hyperplasia and thrombosis at sites of balloon angioplasty or stent placement remains an important clinical problem. It is likely that loss or damage to the arterial endothelium associated with these interventional procedures as well as the rate of its restoration plays a critical role in the extent of restenosis. Migration of arterial endothelial cells from adjacent intact endothelium is the predominant source of cells involved in re-endothelialization of the injured site. In this paper, we review the influence of hemodynamics on endothelial cell migration, both in vivo and in vitro. In addition, we present recent in vitro studies demonstrating the importance of the nature of metal substrates in modulating endothelial cell migration rate. Finally, we review the cellular and molecular mechanisms likely involved in governing endothelial cell migration, and relate them to a possible scenario of endothelial response to injury at sites of arterial intervention. Understanding the important factors regulating endothelial migration may provide insights that will ultimately lead to methods to accelerate endothelial healing and reduce the occurrence of arterial restenosis.
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Journal ArticleDOI
Ning Xu1, Hao Meng1, Tianyi Liu1, Yingli Feng1, Yuan Qi1, Donghuan Zhang1, Honglei Wang1 
TL;DR: Stent-jailing technique reduces IA recurrence more than stent-jack by causing less mechanical forces, angiogenesis and inhibiting TGF-β/Smad2,3,4 signaling in IA patients.
Abstract: Background: Stent-jailing and stent-jack are used for stent-assisted coil embolism (SCE) in intracranial aneurysm (IA) therapy, and cause different incidences of IA recurrence. Angiogenesis strongly correlates with aneurysm accumulation. Stent-jack causes higher mechanical forces in cerebral vessels than stent-jailing. Mechanical forces, as well as TGF-β/Smad2,3,4 signaling pathway, may play an important factor in IA recurrence by affecting angiogenesis. Methods: We explored the effects of stent-jailing or stent-jack technique on IA recurrence by investigating mechanical forces, TGF-β/Smad2,3,4 signaling pathway and the incidence of angiogenesis in IA patients. One-hundred-eighty-one IA patients were assigned into stent-jailing (n = 93) and stent-jacket groups (n = 88). The clinical outcome was evaluated using Glasgow Outcome Score (GOS) and aneurysm occlusion grades. The percentage of CD34+EPCs (releasing pro-angiogenic cytokines) in peripheral blood was measured by flow cytometer. Endothelial cells were separated from cerebral aneurysm and malformed arteries via immunomagnetic cell sorting. Angiogenesis was measured by microvessel density (MVD) using anti-CD34 monoclonal antibody staining before using the stent, immediately after surgery and 2 years later. Meanwhile, the mechanical forces in cerebral vessels were determined by measuring endothelial shear stress (ESS) via a computational method. TGF-β and Smad2,3,4 were measured by real-time qPCR and Western Blot. Tube formation analysis was performed to test the relationship between angiogenesis and TGF-β, and the effects of different techniques on angiogenesis. Results: After a 2-year follow-up, 85 and 81 patients from stent-jailing and stent-jack groups, respectively, completed the experiment. Stent-jailing technique improved GOS and reduced aneurysm occlusion grades higher than the stent-jack technique (P < 0.05). The counts of CD34+EPCs and MVD values in the stent-jailing group were lower than the stent-jack group (P < 0.05). ESS values in sent-jailing group were lower than the stent-jack group (P < 0.05), and positively correlated with MVD values (P < 0.05). TGF-β and Smad2,3,4 levels in sent-jailing group were also lower than the stent-jack group (P < 0.05). TGF-β was associated with angiogenesis incidence and stent-jack caused angiogenesis incidence more than stent-jailing. Conclusion: Stent-jailing technique reduces IA recurrence more than stent-jack by causing less mechanical forces, angiogenesis and inhibiting TGF-β/Smad2,3,4 signaling in IA patients.

8 citations


Cites background from "Static and Flow Conditions: Endothe..."

  • ...The interaction of stents with the cerebral endothelial cells in a controlled environment has been widely reported (Sprague et al., 2017; Tefft et al., 2017; Ter Meer et al., 2017)....

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Journal ArticleDOI
TL;DR: In this paper, the authors studied polymorphic loci of genes encoding endothelin-1 (EDN1 rs5370), ENE receptor (ENE rs5333), Endothelin converting enzyme (ECE1 rs1076669), and endothelial NO synthase (eNOS rs1549758, eNE rs1799983, eNO synthase, and eNO rs2070244) in the context of in-stent restenosis development.
Abstract: Restenosis remains the main complication after percutaneous coronary interventions in patients with coronary heart disease. The causes of its development include, in particular, genetic factors. We studied polymorphic loci of genes encoding endothelin-1 (EDN1 rs5370), endothelin-1 receptor (EDNRA rs5333), endothelin-converting enzyme (ECE1 rs1076669), and endothelial NO synthase (eNOS rs1549758, eNOS rs1799983, and eNOS rs2070244) in the context of in-stent restenosis development. It was found that the analyzed polymorphisms of the endothelin system genes were more significant for patients aged ≥ 65 years, while the polymorphic loci of the endothelial NO synthase gene (eNOS rs1799983 and eNOS rs1549758) were predominantly associated with time of in-stent restenosis. The obtained results can be useful for comprehensive assessment of the restenosis risk factors and the choice of optimal treatment for patients with coronary heart disease before elective surgical intervention.