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内皮损伤抑制剂可保护行冠状动脉旁路移植术患者的静脉内皮细胞的完整性。

Endothelial damage inhibitor preserves the integrity of venous endothelial cells from patients undergoing coronary bypass surgery.

机构信息

Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité (DHZC), Berlin, Germany.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

出版信息

Eur J Cardiothorac Surg. 2023 Dec 1;64(6). doi: 10.1093/ejcts/ezad327.

Abstract

OBJECTIVES

Despite the success of coronary artery bypass graft (CABG) surgery using autologous saphenous vein grafts (SVGs), nearly 50% of patients experience vein graft disease within 10 years of surgery. One contributing factor to early vein graft disease is endothelial damage during short-term storage of SVGs in inappropriate solutions. Our aim was to evaluate the effects of a novel endothelial damage inhibitor (EDI) on SVGs from patients undergoing elective CABG surgery and on venous endothelial cells (VECs) derived from these SVGs.

METHODS

SVGs from 11 patients participating in an ongoing clinical registry (NCT02922088) were included in this study, and incubated with both full electrolyte solution (FES) or EDI for 1 h and then examined histologically. In 8 of 11 patients, VECs were isolated from untreated grafts, incubated with both FES and EDI for 2 h under hypothermic stress conditions and then analysed for activation of an inflammatory phenotype, cell damage and cytotoxicity, as well as endothelial integrity and barrier function.

RESULTS

The EDI was superior to FES in protecting the endothelium in SVGs (74 ± 8% versus 56 ± 8%, P < 0.001). Besides confirming that the EDI prevents apoptosis in SVG-derived VECs, we also showed that the EDI temporarily reduces adherens junctions in VECs while protecting focal adhesions compared to FES.

CONCLUSIONS

The EDI protects the connectivity and function of the SVG endothelium. Our data suggest that the EDI can preserve focal adhesions in VECs during short-term storage after graft harvesting. This might explain the superiority of the EDI in maintaining most of the endothelium in venous CABG surgery conduits.

摘要

目的

尽管使用自体大隐静脉(SVG)进行冠状动脉旁路移植(CABG)手术取得了成功,但近 50%的患者在手术后 10 年内会出现静脉移植物病变。导致早期静脉移植物病变的一个因素是 SVG 在不合适的溶液中短期储存期间内皮细胞受损。我们的目的是评估一种新型内皮损伤抑制剂(EDI)对接受择期 CABG 手术的患者的 SVG 以及源自这些 SVG 的静脉内皮细胞(VEC)的影响。

方法

本研究纳入了正在进行的临床注册研究(NCT02922088)中 11 名患者的 SVG,并将其分别用全电解质溶液(FES)或 EDI 孵育 1 小时,然后进行组织学检查。在 11 名患者中的 8 名患者中,从未处理的移植物中分离出 VECs,在低温应激条件下用 FES 和 EDI 孵育 2 小时,然后分析其炎症表型激活、细胞损伤和细胞毒性以及内皮完整性和屏障功能。

结果

与 FES 相比,EDI 更能保护 SVG 中的内皮(74±8%比 56±8%,P<0.001)。除了证实 EDI 可防止 SVG 衍生的 VECs 凋亡外,我们还发现 EDI 可暂时减少 VECs 中的黏附连接,同时与 FES 相比保护黏着斑。

结论

EDI 可保护 SVG 内皮的连通性和功能。我们的数据表明,EDI 可以在移植物收获后短期储存期间保持 VEC 中的黏着斑。这可能解释了 EDI 在维持静脉 CABG 手术导管中大部分内皮方面的优越性。

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