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让功能障碍重获功能:造血干细胞移植与细胞治疗中的内皮疾病及当前疗法

英文原题:Putting function back in dysfunction: Endothelial diseases and current therapies in hematopoietic stem cell transplantation and cellular therapies.

查看英文原题

Putting function back in dysfunction: Endothelial diseases and current therapies in hematopoietic stem cell transplantation and cellular therapies.

PubMed 2021/08/16(内容时间) Blood Rev Q1 · IF 7.2(JCR 2025)

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中文摘要

内皮功能障碍表现为血管通透性改变,并呈现促血栓和促炎表型,可导致终末器官损伤,与多种疾病病理过程相关。血液系统及肿瘤疾病患者接受造血干细胞移植(HCT)或CAR-T 细胞治疗后出现的并发症,临床表现有重叠;越来越多证据提示这些并发症与内皮功能障碍有关。尽管支持治疗和疗法不断进步,终末器官毒性仍是死亡的主要原因。通过新策略减轻内皮功能障碍,可能改善患者临床结局。多种他汀类药物通过不同分子机制发挥免疫调节和内皮保护等多效作用。在自身免疫病、慢性炎症性疾病和移植物抗宿主病(GVHD)等免疫介导疾病中的近期应用显示出良好前景。本综述介绍GVHD和CAR-T 相关毒性中的内皮功能障碍机制,总结他汀类药物及其他内皮保护剂的现有证据,并提出进一步研究他汀类药物用于预防HCT及CAR-T 相关广泛内皮功能障碍和终末器官损伤的必要性。

展开英文摘要原文

Endothelial dysfunction is characterized by altered vascular permeability and prothrombotic, pro-inflammatory phenotypes. Endothelial dysfunction results in end-organ damage and has been associated with diverse disease pathologies. Complications observed after hematopoietic stem cell transplantation (HCT) and chimeric antigen receptor-T cell (CAR-T) therapy for hematologic and neoplastic disorders share overlapping clinical manifestations and there is increasing evidence linking these complications to endothelial dysfunction. Despite advances in supportive care and treatments, end-organ toxicity remains the leading cause of mortality.

A new strategy to mitigate endothelial dysfunction could lead to improvement of clinical outcomes for patients. Statins have demonstrated pleiotropic effects of immunomodulatory and endothelial protection by various molecular mechanisms. Recent applications in immune-mediated diseases such as autoimmune disorders, chronic inflammatory conditions, and graft-versus-host disease (GVHD) have shown promising results. In this review, we cover the mechanisms underlying endothelial dysfunction in GVHD and CAR-T cell-related toxicities.

We summarize the current knowledge about statins and other agents used as endothelial protectants.

We propose further studies using statins for prophylaxis and prevention of end-organ damage related to extensive endothelial dysfunction in HCT and CAR-T.

论文信息

作者
Sumransub N、El Jurdi N、Chiraphapphaiboon W、Maakaron JE
第一作者单位
Department of Medicine, University of Minnesota, 420 Delaware St. SE MMC 480, Minneapolis, MN 55455, United States of America.United States
通讯作者单位
Department of Medicine, University of Minnesota, 420 Delaware St. SE MMC 480, Minneapolis, MN 55455, United States of America. Electronic address: maaka001@umn.edu.United States
文献类型
综述
期刊
Blood reviews2022 Jan
原文标识
PubMed 34429234 · DOI 10.1016/j.blre.2021.100883