DataSheet1_Urinary extracellular vesicles carry multiple activators and regulators of coagulation.PDF

Cells shape their extracellular milieu by secreting intracellular products into the environment including extracellular vesicles which are lipid-bilayer limited membrane particles. These vesicles carry out a range of functions, including regulation of coagulation, via multiple contributor mechanisms. Urinary extracellular vesicles are secreted by various cells, lining the urinary space, including the nephron and bladder. They are known to have procoagulant properties, however, the details of this function, beyond tissue factor are not well known. The aim of the study was to access the role of urinary extracellular vesicles in impacting coagulation upon supplementation to plasma. This could indicate their physiological function upon kidney injury or pathology. Supplementation to standard human plasma and plasmas deficient in various coagulation factors was used for this purpose, and calibrated automated thrombogram (CAT®) was the major technique applied. We found that these vesicles contain multiple coagulation-related factors, and their lipid composition affects coagulation activities of plasma upon supplementation. Remarkably, these vesicles can restore thrombin generation in FVII, FVIII, FIX and FXI -deficient plasmas. This study explores the multiple roles of urinary extracellular vesicles in coagulation in in vitro blood coagulation and implies their importance in its regulation by several mechanisms.

细胞可通过向胞外分泌包括脂质双层包被膜性颗粒（细胞外囊泡，extracellular vesicles）在内的胞内产物，塑造其所处的细胞外微环境。这类囊泡可通过多种作用机制执行诸多功能，其中包括凝血调控。尿液细胞外囊泡（urinary extracellular vesicles）由衬覆于泌尿腔隙的各类细胞分泌，涵盖肾单位与膀胱的上皮细胞。现有研究表明其具备促凝血活性，但除组织因子（tissue factor）外，该功能的具体细节尚未被充分阐明。本研究旨在探究尿液细胞外囊泡在被补充至血浆后对凝血过程的影响，这或可揭示其在肾损伤或肾脏病理状态下的生理功能。为此，本研究采用标准人血浆及各类凝血因子缺陷血浆开展补加实验，主要检测技术为校准化自动凝血酶生成试验（calibrated automated thrombogram, CAT®）。研究发现，此类囊泡携带多种凝血相关因子，其脂质组成可影响补加后血浆的凝血活性。尤为关键的是，这类囊泡能够恢复凝血因子VII、VIII、IX及XI缺陷血浆中的凝血酶生成水平。本研究探讨了尿液细胞外囊泡在体外凝血过程中的多重调控作用，并提示其通过多种机制参与凝血调控的重要意义。