Farooqui Akhlaq A, Farooqui Tahira, Sun Grace Y, Lin Teng-Nan, Teh Daniel B L, Ong Wei-Yi
Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH 43210, USA.
Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
Biomedicines. 2023 Apr 15;11(4):1181. doi: 10.3390/biomedicines11041181.
Although there is increasing evidence that oxidative stress and inflammation induced by COVID-19 may contribute to increased risk and severity of thromboses, the underlying mechanism(s) remain to be understood. The purpose of this review is to highlight the role of blood lipids in association with thrombosis events observed in COVID-19 patients. Among different types of phospholipases A that target cell membrane phospholipids, there is increasing focus on the inflammatory secretory phospholipase A IIA (sPLA-IIA), which is associated with the severity of COVID-19. Analysis indicates increased sPLA-IIA levels together with eicosanoids in the sera of COVID patients. sPLA could metabolise phospholipids in platelets, erythrocytes, and endothelial cells to produce arachidonic acid (ARA) and lysophospholipids. Arachidonic acid in platelets is metabolised to prostaglandin H2 and thromboxane A, known for their pro-coagulation and vasoconstrictive properties. Lysophospholipids, such as lysophosphatidylcholine, could be metabolised by autotaxin (ATX) and further converted to lysophosphatidic acid (LPA). Increased ATX has been found in the serum of patients with COVID-19, and LPA has recently been found to induce NETosis, a clotting mechanism triggered by the release of extracellular fibres from neutrophils and a key feature of the COVID-19 hypercoagulable state. PLA2 could also catalyse the formation of platelet activating factor (PAF) from membrane ether phospholipids. Many of the above lipid mediators are increased in the blood of patients with COVID-19. Together, findings from analyses of blood lipids in COVID-19 patients suggest an important role for metabolites of sPLA-IIA in COVID-19-associated coagulopathy (CAC).
尽管越来越多的证据表明，由新冠病毒病（COVID-19）诱导的氧化应激和炎症可能会增加血栓形成的风险和严重程度，但其潜在机制仍有待了解。本综述的目的是强调血脂在COVID-19患者血栓形成事件中的作用。在靶向细胞膜磷脂的不同类型磷脂酶A中，炎症分泌型磷脂酶A IIA（sPLA-IIA）越来越受到关注，它与COVID-19的严重程度相关。分析表明，COVID患者血清中的sPLA-IIA水平和类花生酸均升高。sPLA可使血小板、红细胞和内皮细胞中的磷脂代谢，产生花生四烯酸（ARA）和溶血磷脂。血小板中的花生四烯酸代谢为前列腺素H2和血栓素A，它们以促凝血和血管收缩特性而闻名。溶血磷脂，如溶血磷脂酰胆碱，可被自分泌运动因子（ATX）代谢，并进一步转化为溶血磷脂酸（LPA）。在COVID-19患者的血清中发现ATX升高，最近发现LPA可诱导中性粒细胞胞外陷阱形成（NETosis），这是一种由中性粒细胞释放细胞外纤维引发的凝血机制，也是COVID-19高凝状态的一个关键特征。PLA2还可催化膜醚磷脂形成血小板活化因子（PAF）。上述许多脂质介质在COVID-19患者的血液中都有所增加。总之，对COVID-19患者血脂的分析结果表明，sPLA-IIA的代谢产物在COVID-19相关凝血病（CAC）中起重要作用。
