血管生成素-Tie2系统作为脓毒症和急性肺损伤的治疗靶点
The angiopoietin-Tie2 system as a therapeutic target in sepsis and acute lung injury.
作者信息
van der Heijden Melanie, van Nieuw Amerongen Geerten P, Chedamni Sunita, van Hinsbergh Victor W M, Johan Groeneveld A B
机构信息
VU University Medical Center, Institute for Cardiovascular Research, Department of Intensive Care, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
出版信息
Expert Opin Ther Targets. 2009 Jan;13(1):39-53. doi: 10.1517/14728220802626256.
BACKGROUND
Sepsis and acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are life-threatening syndromes characterised by inflammation and increased vascular permeability. Amongst other factors, the angiopoietin-tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) system is involved.
OBJECTIVE
To explore whether the angiopoietin-Tie2 system provides suitable targets for the treatment of sepsis and ALI/ARDS.
METHODS
Original experimental and patient studies on angiopoietins and sepsis/endotoxemia, inflammation, lung injury, hyperpermeability, apoptosis, organ functions and vital outcomes were reviewed.
RESULTS/CONCLUSION: The angiopoietin-Tie2 system controls the responsiveness of the endothelium to inflammatory, hyperpermeability, apoptosis and vasoreactive stimuli. Angiopoietin-2 provokes inflammation and vascular hyperpermeability, while angiopoietin-1 has a protective effect. Targeted angiopoietin-2 inhibition with RNA aptamers or blocking antibodies is a potential anti-inflammatory and anti-vascular hyperpermeability strategy in the treatment of sepsis and ALI/ARDS.
背景
脓毒症和急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）是危及生命的综合征，其特征为炎症反应和血管通透性增加。血管生成素 - 具有免疫球蛋白样和表皮生长因子样结构域2（Tie2）系统等多种因素参与其中。
目的
探讨血管生成素 - Tie2系统是否为脓毒症和ALI/ARDS的治疗提供合适靶点。
方法
回顾了关于血管生成素与脓毒症/内毒素血症、炎症、肺损伤、高通透性、细胞凋亡、器官功能及重要结局的原始实验和患者研究。
结果/结论：血管生成素 - Tie2系统控制内皮细胞对炎症、高通透性、细胞凋亡及血管反应性刺激的反应性。血管生成素 - 2引发炎症和血管高通透性，而血管生成素 - 1具有保护作用。用RNA适体或阻断抗体靶向抑制血管生成素 - 2是治疗脓毒症和ALI/ARDS的潜在抗炎和抗血管高通透性策略。
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