Center for CardioVascular and Nutrition Research (C2VN), INSERM, INRA and Aix-Marseille University, Marseille, France.
Department of Cardiology, North Hospital, Marseille, France.
J Cell Mol Med. 2019 Oct;23(10):6805-6811. doi: 10.1111/jcmm.14564. Epub 2019 Aug 24.
Extracellular vesicles (EV) can transfer cellular molecules for specific intercellular communication with potential relevance in pathological conditions. We searched for the presence in plasma from coronary artery disease (CAD) patients of EV containing the adenosine A receptor (A R), a signalling receptor associated with myocardial ischaemia and whose expression is related to homocysteine (HCy) metabolism. Using protein organic solvent precipitation for plasma EV preparation and Western blotting for protein identification, we found that plasma from CAD patients contained various amounts of EV with ubiquitin bound to A R. Interestingly, the presence of ubiquitinated A R in EV from patients was dependent on hyperhomocysteinemia, the amount being inversely proportional to A R expression in peripheral mononuclear cells in patients with the highest levels of HCy. CEM, a human T cell line, was also found to released EV containing various amounts of ubiquitinated A R in stimulated conditions depending on the hypoxic status and HCy level of culture medium. Together, these data show that ubiquitinated A R-containing EV circulate in the plasma of CAD patients and that this presence is related to hyperhomocysteinemia. A R in plasma EV could be a useful tool for diagnosis and a promising drug for the treatment of CAD.
细胞外囊泡（EV）可以传递细胞分子，实现特定的细胞间通讯，这在病理条件下具有潜在的相关性。我们在冠心病（CAD）患者的血浆中寻找含有腺苷 A 受体（A R）的 EV，A R 是一种与心肌缺血相关的信号受体，其表达与同型半胱氨酸（HCy）代谢有关。我们使用蛋白质有机溶剂沉淀法制备血浆 EV，并通过 Western blot 法进行蛋白质鉴定，发现 CAD 患者的血浆中含有不同数量的与泛素结合的 A R 的 EV。有趣的是，患者 EV 中存在泛素化的 A R 取决于高同型半胱氨酸血症，其数量与患者外周单核细胞中 A R 的表达呈反比，患者的 HCy 水平最高。在受刺激的条件下，根据缺氧状态和培养基中的 HCy 水平，人类 T 细胞系 CEM 也被发现释放含有不同数量泛素化 A R 的 EV。这些数据表明，含泛素化 A R 的 EV 在 CAD 患者的血浆中循环，并且这种存在与高同型半胱氨酸血症有关。血浆 EV 中的 A R 可能是诊断的有用工具，也是治疗 CAD 的有前途的药物。
