Department of Clinical and Biological Sciences, University of Turin, Italy.
Oxid Med Cell Longev. 2021 Apr 15;2021:8886666. doi: 10.1155/2021/8886666. eCollection 2021.
Endothelial cell injury and vascular function strongly correlate with cardiac function following ischemia/reperfusion injury. Several studies indicate that endothelial cells are more sensitive to ischemia/reperfusion compared to cardiomyocytes and are critical mediators of cardiac ischemia/reperfusion injury. HS is involved in the regulation of cardiovascular system homeostasis and can act as a cytoprotectant during ischemia/reperfusion. Activation of ERK1/2 in endothelial cells after HS stimulation exerts an enhancement of angiogenesis while its inhibition significantly decreases HS cardioprotective effects. In this work, we investigated how HS pretreatment for 24 hours prevents the ischemia/reperfusion injury and promotes angiogenesis on microvascular endothelial cells following an ischemia/reperfusion protocol in vitro, using a hypoxic chamber and ischemic buffer to simulate the ischemic event. HS preconditioning positively affected cell viability and significantly increased endothelial cell migration when treated with 1 M HS. Furthermore, mitochondrial function was preserved when cells were preconditioned. Since ERK1/2 phosphorylation was extremely enhanced in ischemia/reperfusion condition, we inhibited ERK both directly and indirectly to verify how HS triggers this pathway in endothelial cells. Taken together, our data suggest that HS treatment 24 hours before the ischemic insult protects endothelial cells from ischemia/reperfusion injury and eventually decreases myocardial injury.
内皮细胞损伤和血管功能与缺血/再灌注损伤后的心脏功能密切相关。几项研究表明，与心肌细胞相比，内皮细胞对缺血/再灌注更为敏感，是心肌缺血/再灌注损伤的关键介质。HS 参与心血管系统稳态的调节，在缺血/再灌注期间可作为细胞保护剂发挥作用。HS 刺激后内皮细胞中 ERK1/2 的激活可增强血管生成，而其抑制则显著降低 HS 的心脏保护作用。在这项工作中，我们使用缺氧室和缺血缓冲液模拟缺血事件，在体外研究了 HS 预处理 24 小时如何预防缺血/再灌注损伤，并促进微血管内皮细胞在缺血/再灌注后血管生成。HS 预处理可显著提高细胞活力和内皮细胞迁移，当用 1 M HS 处理时。此外，细胞的线粒体功能也得到了保留。由于 ERK1/2 的磷酸化在缺血/再灌注条件下极度增强，我们直接和间接抑制 ERK，以验证 HS 如何在内皮细胞中触发这条途径。总之，我们的数据表明，缺血前 24 小时 HS 处理可保护内皮细胞免受缺血/再灌注损伤，最终减少心肌损伤。
