Platelet lipidomics: modern day perspective on lipid discovery and characterization in platelets.

Platelet lipidomics: modern day perspective on lipid discovery and characterization in platelets.
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DOI:
10.1161/circresaha.114.301597
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发表时间:
2014-03-28
影响因子:
20.1
通讯作者:
Watson SP
Watson SP
中科院分区:
医学1区
文献类型:
--
作者:
O'Donnell VB;Murphy RC;Watson SP

文献摘要

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脂类是生物分子的不同家族,在血小板中发挥重要的结构和信号作用。它们的形成和代谢受到酶和信号转导途径的严格控制,它们的失调会导致血小板功能和疾病的严重缺陷。血小板活化与膜脂的显著变化和多种生物活性脂类的形成有关,这些生物活性脂类在止血中发挥重要作用。近年来,新一代脂类的质谱学分析(称为“脂质组学”)已经开始改变我们对这些分子如何参与关键细胞过程的理解。虽然脂质组学在血小板生物学中的应用仍处于初级阶段,但开创性的早期研究已经形成了我们对脂质如何调节血小板生物学的关键方面的知识,包括聚集、形状变化、凝血和脱颗粒,以及血小板产生的脂质如何影响其他细胞,如白细胞和血管壁,从而它们如何调节止血、血管完整性和炎症,以及对包括动脉/深静脉血栓形成和动脉粥样硬化在内的病理的影响。本文将对血小板中脂质的特性进行简要的历史回顾,然后概述新一代脂质组学方法及其在血小板生物学中的最新应用,并展望这一领域的研究前景。主要的血小板调节脂质家族,它们的形成、代谢,以及它们在健康和疾病中的作用,将被总结。
Lipids are diverse families of biomolecules that perform essential structural and signaling roles in platelets. Their formation and metabolism is tightly controlled by enzymes and signal transduction pathways, and their dysregulation leads to significant defects in platelet function and disease. Platelet activation is associated with significant changes to membrane lipids, and formation of diverse bioactive lipids that play essential roles in hemostasis. In recent years, new generation mass spectrometry analysis of lipids (termed “lipidomics”) has begun to alter our understanding of how these molecules participate in key cellular processes. While, the application of lipidomics to platelet biology is still in its infancy, seminal earlier studies have shaped our knowledge of how lipids regulate key aspects of platelet biology, including aggregation, shape change, coagulation and degranulation, as well as how lipids generated by platelets influence other cells, such as leukocytes and the vascular wall, and thus how they regulate hemostasis, vascular integrity and inflammation, as well as contribute to pathologies including arterial/deep vein thrombosis and atherosclerosis. This review will provide a brief historical perspective on the characterization of lipids in platelets, then an overview of the new generation lipidomic approaches, their recent application to platelet biology, and future perspectives for research in this area. The major platelet-regulatory lipid families, their formation, metabolism, and their role in health and disease, will be summarized.