Dept of Intensive Care, Erasme Hospital, Université Libre De Bruxelles, Brussels, Belgium.
Department of Intensive Care, Laboratory of Translational Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Expert Opin Ther Targets. 2021 Sep;25(9):733-748. doi: 10.1080/14728222.2021.1988928. Epub 2021 Oct 22.
Endothelial cells maintain vascular integrity, tone, and patency and have important roles in hemostasis and inflammatory responses. Although some degree of endothelial dysfunction with increased vascular permeability may be necessary to control local infection, excessive dysfunction plays a central role in the pathogenesis of sepsis-related organ dysfunction and failure as it results in dysregulated inflammation, vascular leakage, and abnormal coagulation. The vascular endothelium has thus been proposed as a potential target for therapeutic intervention in patients with sepsis.
Different mechanisms underlying sepsis-related dysfunction of the vascular endothelium are discussed, including glycocalyx shedding, nitrosative stress, and coagulation factors. Potential therapeutic implications of each mechanism are mentioned.
Multiple targets to protect or restore endothelial function have been suggested, but endothelium-driven treatments remain a future potential at present. As some endothelial dysfunction and permeability may be necessary to remove infection and repair damaged tissue, targeting the endothelium may be a particular challenge. Ideally, therapies should be guided by biomarkers related to that specific pathway to ensure they are given only to patients most likely to respond. This enrichment based on biological plausibility and theragnostics will increase the likelihood of a beneficial response in individual patients and enable more personalized treatment.
内皮细胞维持血管完整性、张力和通畅性，在止血和炎症反应中发挥重要作用。尽管一定程度的内皮功能障碍伴增加的血管通透性可能是控制局部感染所必需的，但过度的功能障碍在与脓毒症相关的器官功能障碍和衰竭的发病机制中起着核心作用，因为它导致失调的炎症、血管渗漏和异常凝血。因此，血管内皮已被提议作为脓毒症患者治疗干预的潜在靶点。
讨论了与脓毒症相关的血管内皮功能障碍的不同机制，包括糖萼脱落、硝化应激和凝血因子。提到了每种机制的潜在治疗意义。
已经提出了多种保护或恢复内皮功能的靶点，但目前内皮驱动的治疗仍然是未来的潜在治疗方法。由于去除感染和修复受损组织可能需要一定程度的内皮功能障碍和通透性，因此靶向内皮可能是一个特殊的挑战。理想情况下，治疗应该根据与特定途径相关的生物标志物来指导，以确保仅将其给予最有可能有反应的患者。这种基于生物学合理性和治疗学的富集将增加个体患者获得有益反应的可能性，并能够实现更个性化的治疗。
