Institute of Physiology, University of Luebeck, Luebeck, Germany; Department of Anesthesiology and Intensive Care Medicine, University Medical Centre Schleswig-Holstein Campus Luebeck, University of Luebeck, Luebeck, Germany.
Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy.
Am J Pathol. 2023 Apr;193(4):474-492. doi: 10.1016/j.ajpath.2022.12.009. Epub 2023 Jan 18.
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 exposed in vitro to serum samples collected from patients with AMI. In addition, in situ ECs of ex vivo aorta 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.
内皮细胞（EC）的外层由内皮糖萼（eGC）和皮层（CTX）组成，为血管疾病提供了保护屏障。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，并可能导致心血管事件，如急性心肌梗死（AMI）。本研究调查了 AMI 对内皮细胞纳米力学和功能的影响，以及外源性重组硫酸乙酰肝素聚糖 1（rSyn-1）作为恢复剂的作用。rSyn-1 是 eGC 的主要成分之一，在体外将 EC 暴露于从 AMI 患者中收集的血清样本中。此外，还使用源自 AMI 小鼠模型的离体主动脉制备物中的原位 EC。通过基于原子力显微镜的纳米压痕测量、荧光染色和对小鼠心脏的组织学检查来定量这些效果。AMI 血清样本损伤了 eGC/CTX，并增加了单核细胞在内皮表面的黏附。特别是过敏毒素 C3a 和 C5a 在这些过程中发挥了重要作用。rSyn-1 处理可预防内皮功能障碍。在心肌梗死的小鼠模型中，rSyn-1 的预处理减轻了 eGC/CTX 的恶化，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表明存在功能益处。这些结果提供了对 AMI 诱导的内皮功能障碍的潜在机制的新见解，并为 rSyn-1 在 AMI 后治疗中的益处的未来研究提供了思路。
