Aminophospholipids (aPL) such as phosphatidylserine (PS) are essential for supporting the activity of coagulation factors, circulating platelets and blood cells. Phosphatidylthreonine (PT) is an aPL previously reported in eukaryotic parasites and animal cell cultures, but not yet in human tissues. Here, we evaluated whether PT is present in blood cells and characterized its ability to support coagulation. Several PT molecular species were detected in human blood, washed platelets, extracellular vesicles (EV), and isolated leukocytes from healthy volunteers using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The ability of PT to support coagulation was demonstrated in vitro using biochemical and biophysical assays. In liposomes, PT supported prothrombinase activity in the presence and absence of PS. PT nanodiscs strongly bound FVa and lactadherin (nM affinity), but poorly bound prothrombin and FX, suggesting that PT supports prothrombinase through recruitment of FVa. PT liposomes bearing tissue factor poorly generated thrombin in platelet poor plasma, indicating that PT poorly supports extrinsic tenase activity. On platelet activation, PT is externalized and partially metabolized. Last, PT was significantly higher in platelets and EV from patients with coronary artery disease, than in healthy controls. In summary, PT is present in human blood, binds FVa and lactadherin, supports coagulation in vitro through FVa binding, and is elevated in atherosclerotic vascular disease. Our studies reveal a new phospholipid sub-class, that contributes to the pro-coagulant membrane, and may support thrombosis in patients at elevated risk.

中文翻译：

---

磷脂酰苏氨酸是一种在人体血液中检测到的促凝血脂质，在冠状动脉疾病中升高。


磷脂酰丝氨酸 (PS) 等氨基磷脂 (aPL) 对于支持凝血因子、循环血小板和血细胞的活性至关重要。磷脂酰苏氨酸 (PT) 是一种 aPL，之前曾在真核寄生虫和动物细胞培养物中报道过，但尚未在人体组织中报道过。在这里，我们评估了血细胞中是否存在 PT 并表征了其支持凝血的能力。使用液相色谱-串联质谱 (LC-MS/MS) 在人类血液、洗涤的血小板、细胞外囊泡 (EV) 和从健康志愿者中分离的白细胞中检测到多种 PT 分子种类。使用生化和生物物理测定在体外证明了 PT 支持凝血的能力。在脂质体中，无论 PS 存在还是不存在，PT 都支持凝血酶原酶活性。 PT 纳米圆盘强烈结合 FVa 和乳粘素（nM 亲和力），但与凝血酶原和 FX 结合较差，表明 PT 通过募集 FVa 支持凝血酶原。携带组织因子的 PT 脂质体在贫血小板血浆中很难产生凝血酶，表明 PT 很难支持外源性 tenase 活性。血小板激活后，PT 被外化并部分代谢。最后，冠状动脉疾病患者的血小板和 EV 的 PT 显着高于健康对照。总之，PT存在于人体血液中，与FVa和乳粘素结合，通过FVa结合支持体外凝血，并且在动脉粥样硬化性血管疾病中升高。我们的研究揭示了一种新的磷脂亚类，它有助于促凝血膜，并可能支持高危患者的血栓形成。