Department of Cardiology, Angiology and Cardiovascular Medicine, Eberhard Karls University of Tübingen, Germany; DFG Heisenberg Group Thrombocardiology, Eberhard Karls University of Tübingen, Germany.
Department of Analytical Chemistry, University of Vienna, Austria.
Pharmacol Ther. 2022 Sep;237:108258. doi: 10.1016/j.pharmthera.2022.108258. Epub 2022 Jul 29.
The function of platelets - and thereby the balance between thrombosis and hemostasis - critically depends on their lipid composition. At the same time, platelets are capable of interacting with inflammatory cells by releasing lipids in a paracrine manner. Over the years, many studies have emphasized the importance of both, membrane and signaling lipids, in the signaling pathways underlying arterial thrombosis and chronic inflammation. In line with this, an imbalance of platelet lipid homeostasis is associated with thrombo-inflammatory diseases such as acute coronary syndrome. By establishing quantitative platelet lipidomic analysis, an opportunity has arisen to deepen our knowledge about platelet lipids regulating thrombo-inflammation and vice versa. Past and future investigations in this upcoming field are of great clinical importance since they will presumably pave the way for the identification of novel biomarkers. In addition, targeting specific regulators of the platelet lipid metabolism is a promising strategy to receive both anti-thrombotic and anti-inflammatory therapeutics and could be beneficial to a wide variety of patients with vascular thrombo-inflammatory diseases. This review summarizes the latest scientific findings in the field of platelet lipidomics research and does so by focusing on the metabolism of sphingolipids, oxylipins and phosphoinositides, which are affected by dynamic modifications in a pathophysiological manner. Further, this review elucidates the impact of these platelet lipids on thrombo-inflammatory cardiovascular diseases and highlights potential diagnostic and therapeutic targets.
血小板的功能——以及血栓形成和止血之间的平衡——严重依赖于其脂质组成。同时，血小板能够通过旁分泌的方式释放脂质来与炎症细胞相互作用。多年来，许多研究强调了膜和信号脂质在动脉血栓形成和慢性炎症的信号通路中的重要性。与此相一致的是，血小板脂质稳态的失衡与血栓炎症性疾病如急性冠脉综合征有关。通过建立定量血小板脂质组学分析，我们有机会深入了解调节血栓炎症的血小板脂质，反之亦然。这一即将到来的领域的过去和未来的研究具有重要的临床意义，因为它们可能为识别新的生物标志物铺平道路。此外，靶向血小板脂质代谢的特定调节剂是一种有前途的抗血栓和抗炎治疗策略，可能对多种血管血栓炎症性疾病患者有益。本综述总结了血小板脂质组学研究领域的最新科学发现，重点关注了受病理生理方式下动态修饰影响的鞘脂、氧化脂质和磷酸肌醇的代谢。此外，本综述阐明了这些血小板脂质对血栓炎症性心血管疾病的影响，并强调了潜在的诊断和治疗靶点。
