Heparan sulfates and heparan sulfate binding proteins in sepsis.
Heparan sulfates and heparan sulfate binding proteins in sepsis.
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DOI：
10.3389/fmolb.2023.1146685
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发表时间：
2023
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
硫酸乙酰肝素 (HS) 是覆盖内皮细胞的糖萼的主要成分，并通过与多种硫酸乙酰肝素结合蛋白 (HSBP) 相互作用来调节血管稳态。脓毒症期间，乙酰肝素酶增加并诱导 HS 脱落。该过程导致糖萼降解，加剧脓毒症中的炎症和凝血。在某些情况下，循环的硫酸乙酰肝素片段可以通过中和失调的硫酸乙酰肝素结合蛋白或促炎分子来充当宿主防御系统。了解健康和脓毒症中的硫酸乙酰肝素和硫酸乙酰肝素结合蛋白对于破译脓毒症中失调的宿主反应和推进药物开发至关重要。在这篇综述中，我们将概述目前对脓毒症条件下糖萼中 HS 的认识，以及功能失调的硫酸乙酰肝素结合蛋白作为潜在药物靶点，特别是高迁移率族蛋白 1 (HMGB1) 和组蛋白。此外，还将讨论基于硫酸乙酰肝素或与硫酸乙酰肝素相关的几种候选药物，例如乙酰肝素酶抑制剂或肝素结合蛋白（HBP）的最新进展。通过应用化学或化学酶方法，最近用结构确定的硫酸乙酰肝素揭示了硫酸乙酰肝素和硫酸乙酰肝素结合蛋白之间的结构-功能关系。这种同质硫酸乙酰肝素可以进一步促进硫酸乙酰肝素在败血症中的作用的研究和基于碳水化合物的疗法的开发。
Heparan sulfates (HSs) are the main components in the glycocalyx which covers endothelial cells and modulates vascular homeostasis through interactions with multiple Heparan sulfate binding proteins (HSBPs). During sepsis, heparanase increases and induces HS shedding. The process causes glycocalyx degradation, exacerbating inflammation and coagulation in sepsis. The circulating heparan sulfate fragments may serve as a host defense system by neutralizing dysregulated Heparan sulfate binding proteins or pro-inflammatory molecules in certain circumstances. Understanding heparan sulfates and heparan sulfate binding proteins in health and sepsis is critical to decipher the dysregulated host response in sepsis and advance drug development. In this review, we will overview the current understanding of HS in glycocalyx under septic condition and the dysfunctional heparan sulfate binding proteins as potential drug targets, particularly, high mobility group box 1 (HMGB1) and histones. Moreover, several drug candidates based on heparan sulfates or related to heparan sulfates, such as heparanase inhibitors or heparin-binding protein (HBP), will be discussed regarding their recent advances. By applying chemical or chemoenzymatic approaches, the structure-function relationship between heparan sulfates and heparan sulfate binding proteins is recently revealed with structurally defined heparan sulfates. Such homogenous heparan sulfates may further facilitate the investigation of the role of heparan sulfates in sepsis and the development of carbohydrate-based therapy.
影响因子：
4.7
作者：
Arnold K;Liao YE;Liu J
通讯作者：
Liu J
影响因子：
3.2
作者：
Mauro, Katie D.;Lambert, Michele P.;Kowalska, M. Anna;Thawley, Vincent J.;Poncz, Mortimer;Otto, Cynthia M.
通讯作者：
Otto, Cynthia M.
DOI：
10.1016/j.bbalip.2021.159064
发表时间：
2022-01
期刊：
Biochimica et biophysica acta. Molecular and cell biology of lipids
影响因子：
--
作者：
Jayaraman S;Pérez A;Miñambres I;Sánchez-Quesada JL;Gursky O
通讯作者：
Gursky O