Endothelial biomarkers in human sepsis: pathogenesis and prognosis for ARDS.
Endothelial biomarkers in human sepsis: pathogenesis and prognosis for ARDS.
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DOI：
10.1177/2045894018769876
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发表时间：
2018-04
影响因子：
2.6
通讯作者：
Matthay MA
中科院分区：
文献类型：
--
作者：
Hendrickson CM;Matthay MA
小型和大型动物脓毒症的实验模型以及各种体外制剂已经建立了几种驱动内皮损伤的基本机制。本综述的重点是从脓毒症患者内皮损伤和炎症血浆生物标志物的临床研究结果中可以学到什么。有充分证据表明，多种内皮损伤生物标志物（包括血管性血友病因子抗原 (VWF)、血管生成素-2 (Ang-2) 和可溶性 fms 样酪氨酸激酶 1 (sFLT-1)）以及炎症生物标志物（尤其是白介素-8 (IL-8) 和可溶性肿瘤坏死因子受体 (sTNFr)）的血浆水平升高，可识别脓毒症患者的死亡率较高。还有一些数据表明，内皮生物标志物水平升高可以识别哪些非肺脓毒症患者会发展为急性呼吸窘迫综合征（ARDS）。如果将ARDS患者分为间接肺损伤患者和直接肺损伤患者，那么间接损伤中的内皮生物标志物水平升高与直接肺损伤患者中的炎症和肺泡上皮损伤标志物水平升高存在相关性。新的研究表明，生物标志物和临床标志物的结合可能能够将 ARDS 患者分为低炎症表型和高炎症表型，这可能对液体疗法的治疗反应产生影响。综上所述，本文综述的研究支持微循环在脓毒症后 ARDS 的发病机制和预后中的主要作用。通过分子模式识别的生物学差异可以解释治疗效果的异质性，而这些异质性不能仅通过临床因素来解释。
Experimental models of sepsis in small and large animals and a variety of in vitro preparations have established several basic mechanisms that drive endothelial injury. This review is focused on what can be learned from the results of clinical studies of plasma biomarkers of endothelial injury and inflammation in patients with sepsis. There is excellent evidence that elevated plasma levels of several biomarkers of endothelial injury, including von Willebrand factor antigen (VWF), angiopoietin-2 (Ang-2), and soluble fms-like tyrosine kinase 1 (sFLT-1), and biomarkers of inflammation, especially interleukin-8 (IL-8) and soluble tumor necrosis factor receptor (sTNFr), identify sepsis patients with a higher mortality. There are also some data that elevated levels of endothelial biomarkers can identify which patients with non-pulmonary sepsis will develop acute respiratory distress syndrome (ARDS). If ARDS patients are divided among those with indirect versus direct lung injury, then there is an association of elevated levels of endothelial biomarkers in indirect injury and markers of inflammation and alveolar epithelial injury in patients with direct lung injury. New research suggests that the combination of biologic and clinical markers may make it possible to segregate patients with ARDS into hypo- versus hyper-inflammatory phenotypes that may have implications for therapeutic responses to fluid therapy. Taken together, the studies reviewed here support a primary role of the microcirculation in the pathogenesis and prognosis of ARDS after sepsis. Biological differences identified by molecular patterns could explain heterogeneity of treatment effects that are not explained by clinical factors alone.