Endothelial Glycocalyx and Cardiomyocyte Damage Is Prevented by Recombinant Syndecan-1 in Acute Myocardial Infarction.
Endothelial Glycocalyx and Cardiomyocyte Damage Is Prevented by Recombinant Syndecan-1 in Acute Myocardial Infarction.
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重组 Syndecan-1 可预防急性心肌梗塞中的内皮糖萼和心肌细胞损伤。
DOI：
10.1016/j.ajpath.2022.12.009
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Kusche-Vihrog,Kristina
中科院分区：
文献类型：
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作者：
Vahldieck,Carl;Cianflone,Eleonora;Fels,Benedikt;Löning,Samuel;Depelmann,Patrik;Sabatino,Jolanda;Salerno,Nadia;Karsten,ChristianM;Torella,Daniele;Weil,Joachim;Sun,Dong;Goligorsky,MichaelS;Kusche-Vihrog,Kristina
由内皮糖萼（eGC）和皮质（CTX）组成的内皮细胞（EC）的外层提供针对血管疾病的保护屏障。其机械性能的结构和功能损伤被认为是内皮功能障碍的标志，并可导致心血管事件，如急性心肌梗死（AMI）。本研究调查了AMI对内皮纳米力学和功能的影响，以及使用外源性重组多配体蛋白聚糖-1（rSyn-1）（eGC的主要成分）作为恢复剂。将内皮细胞体外暴露于AMI患者血清中。此外，采用源自AMI小鼠模型的体内主动脉制备物的原位EC。通过使用基于原子力显微镜的纳米压痕测量、荧光染色和小鼠心脏的组织学检查来量化效果。AMI血清样本损害eGC/CTX和增强单核细胞粘附到内皮表面。特别是，过敏毒素C3 a和C5 a在这些过程中发挥了重要作用。rSyn-1治疗可以预防内皮功能的损害。在心肌梗死的小鼠模型中，用rSyn-1预处理减轻了eGC/CTX恶化，并在组织学分析中减少了心肌细胞损伤。然而，超声心动图测量并未显示功能获益。这些结果为AMI诱导的内皮功能障碍的潜在机制提供了新的见解，并为未来研究rSyn-1在AMI后治疗中的益处提供了前景。
The outer layer of endothelial cells (ECs), consisting of the endothelial glycocalyx (eGC) and the cortex (CTX), provides a protective barrier against vascular diseases. Structural and functional impairments of their mechanical properties are recognized as hallmarks of endothelial dysfunction and can lead to cardiovascular events, such as acute myocardial infarction (AMI). This study investigated the effects of AMI on endothelial nanomechanics and function and the use of exogenous recombinant syndecan-1 (rSyn-1), a major component of the eGC, as recovering agent. ECs were exposedin vitroto serum samples collected from patients with AMI. In addition,in situECs ofex vivoaorta preparations derived from a mouse model for AMI were employed. Effects were quantified by using atomic force microscopy–based nanoindentation measurements, fluorescence staining, and histologic examination of the mouse hearts. AMI serum samples damaged eGC/CTX and augmented monocyte adhesion to the endothelial surface. In particular, the anaphylatoxins C3a and C5a played an important role in these processes. The impairment of endothelial function could be prevented by rSyn-1 treatment. In the mouse model of myocardial infarction, pretreatment with rSyn-1 alleviated eGC/CTX deterioration and reduced cardiomyocyte damage in histologic analyses. However, echocardiographic measurements did not indicate a functional benefit. These results provide new insights into the underlying mechanisms of AMI-induced endothelial dysfunction and perspectives for future studies on the benefit of rSyn-1 in post-AMI treatment.