Cardiovascular Program ICCC, Research Institute of Hospital Santa Creu i Sant Pau, IIB Sant Pau, 08049 Barcelona, Spain.
Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain.
Int J Mol Sci. 2023 Jul 23;24(14):11824. doi: 10.3390/ijms241411824.
Circulating extracellular microvesicles (cEVs) are characterised by presenting surface antigens of parental cells. Since their biogenesis involves the translocation of phosphatidylserine (PS) from the inner to the outer leaflet of the plasma membrane, exposed PS has been considered as a recognition hallmark of cEVs. However, not all cEVs externalise PS. In this study, we have phenotypically and quantitatively characterised cEVs by flow cytometry, paying special attention to the proportions of PS in chronic heart failure patients (cHF; = 119) and a reference non-HF group ( = 21). PS-cEVs were predominantly found in both groups. Parental markers showed differential pattern depending on the PS exposure. Endothelium-derived and connexin 43-rich cEVs were mainly PS-cEVs and significantly increased in cHF. On the contrary, platelet-derived cEVs were mostly PS and were increased in the non-HF group. We observed similar levels of PS- and PS-cEVs in non-HF subjects when analysing immune cell-derived Evs, but there was a subset-specific difference in cHF patients. Indeed, those cEVs carrying CD45, CD29, CD11b, and CD15 were mainly PS-cEVs, while those carrying CD14, CD3, and CD56 were mainly PS-cEVs. In conclusion, endothelial and red blood cells are stressed in cHF patients, as detected by a high shedding of cEVs. Despite PS-cEVs and PS-cEVs representing two distinct cEV populations, their release and potential function as both biomarkers and shuttles for cell communication seem unrelated to their PS content.
循环细胞外微泡 (cEVs) 的特征在于呈现亲本细胞的表面抗原。由于它们的生物发生涉及磷脂酰丝氨酸 (PS) 从质膜的内叶到外叶的易位，因此暴露的 PS 被认为是 cEVs 的识别标志。然而，并非所有的 cEVs 都外化 PS。在这项研究中，我们通过流式细胞术对 cEVs 进行了表型和定量特征分析，特别关注慢性心力衰竭患者 (cHF; n = 119) 和参考非 HF 组 (n = 21) 中 PS 的比例。PS-cEVs 在两组中均占主导地位。亲本标志物的暴露表现出不同的模式。内皮细胞衍生和连接蛋白 43 丰富的 cEVs 主要是 PS-cEVs，在 cHF 中显著增加。相反，血小板衍生的 cEVs 主要是 PS，在非 HF 组中增加。当分析免疫细胞衍生的 Evs 时，我们观察到非 HF 受试者中 PS-和 PS-cEVs 的水平相似，但在 cHF 患者中存在亚群特异性差异。事实上，那些携带 CD45、CD29、CD11b 和 CD15 的 cEVs 主要是 PS-cEVs，而那些携带 CD14、CD3 和 CD56 的 cEVs 主要是 PS-cEVs。总之，在 cHF 患者中，内皮细胞和红细胞受到压力，这可通过 cEVs 的大量释放检测到。尽管 PS-cEVs 和 PS-cEVs 代表两种不同的 cEV 群体，但它们的释放及其作为生物标志物和细胞通讯载体的潜在功能似乎与其 PS 含量无关。
