Department of Cardiology, Charité-Universitätsmedizin Berlin, Germany.
German Center for Cardiovascular Research (DZHK), Germany.
Eur J Prev Cardiol. 2021 Oct 25;28(13):1467-1474. doi: 10.1177/2047487320919894. Epub 2020 May 7.
Extracellular vesicles are released upon cellular activation and mediate inter-cellular communication. Individual species of extracellular vesicles might have divergent roles in vascular homeostasis and may show different responses to therapies such as exercise training.
We examine endothelial effects of medium-size and small extracellular vesicles from the same individual with or without chronic coronary syndrome, and in chronic coronary syndrome patients participating in a four-week high-intensity interval training intervention.
Human aortic endothelial cells were exposed to medium-size extracellular vesicles and small extracellular vesicles isolated from plasma samples of study participants. Endothelial cell survival, activation and re-endothelialisation capacity were assessed by respective staining protocols. Extracellular vesicles were quantified by nanoparticle tracking analysis and flow cytometry. Extracellular vesicle microRNA expression was quantified by realtime-quantitative polymerase chain reaction.
In patients with chronic coronary syndrome (n = 25), plasma counts of leukocyte-derived medium-size extracellular vesicles were higher than in age-matched healthy controls (n = 25; p = 0.04) and were reduced by high-intensity interval training (n = 15; p = 0.01 vs baseline). Re-endothelialisation capacity was promoted by medium-size extracellular vesicles from controls, but not by medium-size extracellular vesicles from chronic coronary syndrome patients. High-intensity interval training for 4 weeks enhanced medium-size extracellular vesicle-mediated support of in vitro re-endothelialisation. Small extracellular vesicles from controls or chronic coronary syndrome patients increased endothelial cell death and reduced repair functions and were not affected by high-intensity interval training.
The present study demonstrates that medium-size extracellular vesicles and small extracellular vesicles differentially affect endothelial cell survival and repair responses. This equilibrium is unbalanced in patients with chronic coronary syndrome where leukocyte-derived medium-size extracellular vesicles are increased leading to a loss of medium-size extracellular vesicle-mediated endothelial repair. High-intensity interval training partially restored medium-size extracellular vesicle-mediated endothelial repair, underlining its use in cardiovascular prevention and therapy to improve endothelial function.
细胞激活时会释放细胞外囊泡，介导细胞间通讯。不同种类的细胞外囊泡在血管稳态中可能具有不同的作用，并且对治疗方法（如运动训练）的反应可能不同。
我们检查了来自同一个体的中等大小和小细胞外囊泡对内皮细胞的影响，这些个体患有或不患有慢性冠状动脉综合征，以及患有慢性冠状动脉综合征的患者参加为期四周的高强度间歇训练干预。
将人主动脉内皮细胞暴露于从研究参与者的血浆样本中分离的中等大小细胞外囊泡和小细胞外囊泡。通过各自的染色方案评估内皮细胞的存活、激活和再内皮化能力。通过纳米颗粒跟踪分析和流式细胞术定量细胞外囊泡。通过实时定量聚合酶链反应定量细胞外囊泡微 RNA 表达。
在患有慢性冠状动脉综合征的患者（n=25）中，白细胞衍生的中等大小细胞外囊泡的血浆计数高于年龄匹配的健康对照组（n=25；p=0.04），并且通过高强度间歇训练（n=15；p=0.01 与基线相比）降低。对照来源的中等大小细胞外囊泡促进了再内皮化能力，但慢性冠状动脉综合征患者来源的中等大小细胞外囊泡则不然。4 周的高强度间歇训练增强了中等大小细胞外囊泡介导的体外再内皮化支持。对照或慢性冠状动脉综合征患者的小细胞外囊泡增加了内皮细胞死亡并降低了修复功能，并且不受高强度间歇训练的影响。
本研究表明，中等大小细胞外囊泡和小细胞外囊泡对内皮细胞存活和修复反应的影响不同。在慢性冠状动脉综合征患者中，这种平衡被打破，白细胞衍生的中等大小细胞外囊泡增加，导致中等大小细胞外囊泡介导的内皮修复丧失。高强度间歇训练部分恢复了中等大小细胞外囊泡介导的内皮修复，强调了其在心血管预防和治疗中的应用，以改善内皮功能。
