Role of Extracellular Vesicles in Pulmonary Arterial Hypertension Modulation of Pulmonary Endothelial Function and Angiogenesis
Role of Extracellular Vesicles in Pulmonary Arterial Hypertension Modulation of Pulmonary Endothelial Function and Angiogenesis
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DOI：
10.1161/atvbaha.120.314152
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发表时间：
2020-09-01
影响因子：
8.7
通讯作者：
Christersson, Christina
中科院分区：
文献类型：
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作者：
Khandagale, Avinash;Aberg, Mikael;Christersson, Christina
目的：细胞外囊泡（EVs）具有细胞间通讯功能。目的是表征肺动脉高压（PAH）患者的循环EV，并探讨这些EV是否有助于内皮激活和血管生成。方法和结果：PAH患者（n=70）和健康对照（HC; n=20）被纳入本横断面研究。表征EV，并将人肺内皮细胞（hPAEC）与纯化的EV孵育。分析内皮细胞活性和促血管生成标志物。对hPAEC进行管形成分析，并评价PSGL-1（P-选择素糖蛋白配体1）的参与。PAH患者血液中的CD 62 P（+）、CD 144（+）和CD 235 a EV数量高于HC患者。PAH和HC EV中有13种蛋白表达不同，其中补体片段C1 q是PAH EV中最显著升高的蛋白（P=0.0009）。在EV内化hPAECs后，与HC EV相比，更多PAH EV逃避溶酶体（P
Objective: Extracellular vesicles (EVs) have the potential to act as intercellular communicators. The aims were to characterize circulating EVs in patients with pulmonary arterial hypertension (PAH) and to explore whether these EVs contribute to endothelial activation and angiogenesis. Approach and Results: Patients with PAH (n=70) and healthy controls (HC; n=20) were included in this cross-sectional study. EVs were characterized and human pulmonary endothelial cells (hPAECs) were incubated with purified EVs. Endothelial cell activity and proangiogenic markers were analyzed. Tube formation analysis was performed for hPAECs, and the involvement of PSGL-1 (P-selectin glycoprotein ligand 1) was evaluated. The numbers of CD62P(+), CD144(+), and CD235a EVs were higher in blood from PAH compared with HC. Thirteen proteins were differently expressed in PAH and HC EVs, where complement fragment C1q was the most significantly elevated protein (P=0.0009) in PAH EVs. Upon EVs-internalization in hPAECs, more PAH compared with HC EVs evaded lysosomes (P