Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Department of Medicine, Denver Health Medical Center, Denver, Colorado.
Semin Thromb Hemost. 2021 Apr;47(3):274-282. doi: 10.1055/s-0041-1725064. Epub 2021 Apr 1.
There is increasing recognition of the importance of the endothelial glycocalyx and its in vivo manifestation, the endothelial surface layer, in vascular homeostasis. Heparan sulfate proteoglycans (HSPGs) are a major structural constituent of the endothelial glycocalyx and serve to regulate vascular permeability, microcirculatory tone, leukocyte and platelet adhesion, and hemostasis. During sepsis, endothelial HSPGs are shed through the induction of "sheddases" such as heparanase and matrix metalloproteinases, leading to loss of glycocalyx integrity and consequent vascular dysfunction. Less well recognized is that glycocalyx degradation releases HSPG fragments into the circulation, which can shape the systemic consequences of sepsis. In this review, we will discuss (1) the normal, homeostatic functions of HSPGs within the endothelial glycocalyx, (2) the pathological changes in HSPGs during sepsis and their consequences on the local vascular bed, and (3) the systemic consequences of HSPG degradation. In doing so, we will identify potential therapeutic targets to improve vascular function during sepsis as well as highlight key areas of uncertainty that require further mechanistic investigation.
人们越来越认识到内皮糖萼及其体内表现形式——内皮表面层在血管稳态中的重要性。硫酸乙酰肝素蛋白聚糖 (HSPGs) 是内皮糖萼的主要结构成分，可调节血管通透性、微循环张力、白细胞和血小板黏附以及止血。在败血症期间，通过诱导“脱落酶”（如肝素酶和基质金属蛋白酶），内皮 HSPGs 脱落，导致糖萼完整性丧失，进而导致血管功能障碍。但人们认识不足的是，糖萼降解会将 HSPG 片段释放到循环中，从而影响败血症的全身后果。在这篇综述中，我们将讨论 (1) HSPGs 在正常内皮糖萼中的稳态功能，(2) 败血症期间 HSPGs 的病理变化及其对局部血管床的影响，以及 (3) HSPG 降解的全身后果。通过这样做，我们将确定在败血症期间改善血管功能的潜在治疗靶点，并强调需要进一步进行机制研究的关键不确定性领域。
