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并行微加工支架槽对内皮细胞迁移、增殖和功能的影响:冠状动脉猪模型愈合反应的体内相关性研究。

Impact of parallel micro-engineered stent grooves on endothelial cell migration, proliferation, and function: an in vivo correlation study of the healing response in the coronary swine model.

机构信息

University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

出版信息

Circ Cardiovasc Interv. 2012 Aug 1;5(4):499-507. doi: 10.1161/CIRCINTERVENTIONS.111.967901. Epub 2012 Jul 3.

DOI:10.1161/CIRCINTERVENTIONS.111.967901
PMID:22763346
Abstract

BACKGROUND

Stent luminal surface characteristics influence surface endothelialization. We hypothesize that luminal stent microgrooves created in the direction of coronary flow accelerate endothelial cell migration, resulting in lower levels of neointimal formation.

METHODS AND RESULTS

Surface coverage efficiency was evaluated in vitro by allowing human aortic endothelial cells (HAEC) to migrate onto microgrooved (G) or smooth (NG) surfaces. HAEC functionality was assessed by proliferation rate, apoptosis rate, nitric oxide production, and inflammatory markers TNF-α and VCAM-1 expression. Early endothelialization and restenosis studies were performed using the porcine coronary injury model. Stainless steel stents of identical design with (GS) and without (NGS) luminal microgrooves were used. The commercially available Multi-Link Vision (MLVS) stent of identical design was used as a control. The degree of GS and NGS surface endothelialization was compared at 3 days. Biocompatibility and tissue response outcomes were evaluated at 28 days. The in vitro study demonstrated that at 7 days the presence of surface microgrooves increased HAEC migration distance >2-fold. Cell proliferation rate and nitric oxide production were increased and apoptosis rate was decreased. There was no difference in inflammatory marker expression. At 3 days, coronary artery stent endothelialization was significantly increased in GS compared with NGS (81.3% versus 67.5%, P=0.0002). At 28 days, GS exhibited lower neointimal thickness compared with either NGS (21.1%, P=0.011) or MLVS (40.8%, P=0.014).

CONCLUSION

Parallel microgrooves on coronary stent luminal surfaces promote endothelial cell migration and positively influence endothelial cell function, resulting in decreased neointimal formation in the porcine coronary injury model.

摘要

背景

支架管腔表面特性影响表面内皮化。我们假设在冠状动脉血流方向上形成的管腔支架微槽加速内皮细胞迁移,从而导致新生内膜形成水平降低。

方法和结果

通过允许人主动脉内皮细胞(HAEC)迁移到微槽(G)或光滑(NG)表面,在体外评估表面覆盖效率。通过增殖率、凋亡率、一氧化氮产生和炎症标志物 TNF-α和 VCAM-1 的表达来评估 HAEC 的功能。使用猪冠状动脉损伤模型进行早期内皮化和再狭窄研究。使用具有(GS)和不具有(NGS)管腔微槽的相同设计的不锈钢支架。使用相同设计的商业上可获得的 Multi-Link Vision(MLVS)支架作为对照。在第 3 天比较 GS 和 NGS 表面内皮化的程度。在第 28 天评估生物相容性和组织反应结果。体外研究表明,在第 7 天,表面微槽的存在使 HAEC 的迁移距离增加了 2 倍以上。细胞增殖率和一氧化氮的产生增加,而凋亡率降低。炎症标志物的表达没有差异。在第 3 天,GS 组与 NGS 组相比,冠状动脉支架内皮化明显增加(81.3%比 67.5%,P=0.0002)。在第 28 天,GS 组与 NGS 组(21.1%,P=0.011)或 MLVS 组(40.8%,P=0.014)相比,新生内膜厚度较低。

结论

冠状动脉支架管腔表面的平行微槽促进内皮细胞迁移,并对内皮细胞功能产生积极影响,从而减少猪冠状动脉损伤模型中的新生内膜形成。

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