Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, United States of America.
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, United States of America; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI, United States of America.
Pharmacol Ther. 2023 Jun;246:108420. doi: 10.1016/j.pharmthera.2023.108420. Epub 2023 Apr 24.
Platelets are small, anucleate cells in the blood that play a crucial role in the hemostatic response but are also implicated in the pathophysiology of cardiovascular disease. It is widely appreciated that polyunsaturated fatty acids (PUFAs) play an integral role in the function and regulation of platelets. PUFAs are substrates for oxygenase enzymes cyclooxygenase-1 (COX-1), 5-lipoxygenase (5-LOX), 12-lipoxygenase (12-LOX) and 15-lipoxygenase (15-LOX). These enzymes generate oxidized lipids (oxylipins) that exhibit either pro- or anti-thrombotic effects. Although the effects of certain oxylipins, such as thromboxanes and prostaglandins, have been studied for decades, only one oxylipin has been therapeutically targeted to treat cardiovascular disease. In addition to the well-known oxylipins, newer oxylipins that demonstrate activity in the platelet have been discovered, further highlighting the expansive list of bioactive lipids that can be used to develop novel therapeutics. This review outlines the known oxylipins, their activity in the platelet, and current therapeutics that target oxylipin signaling.
血小板是血液中的一种无核小细胞，在止血反应中起着至关重要的作用，但也与心血管疾病的病理生理学有关。人们普遍认为，多不饱和脂肪酸（PUFAs）在血小板的功能和调节中起着不可或缺的作用。PUFAs 是加氧酶酶环加氧酶-1（COX-1）、5-脂加氧酶（5-LOX）、12-脂加氧酶（12-LOX）和 15-脂加氧酶（15-LOX）的底物。这些酶生成氧化脂质（氧化脂质），具有促血栓或抗血栓作用。尽管某些氧化脂质，如血栓素和前列腺素，已经研究了几十年，但只有一种氧化脂质被专门用于治疗心血管疾病。除了众所周知的氧化脂质外，还发现了在血小板中具有活性的新型氧化脂质，这进一步强调了可以用于开发新型治疗方法的广泛的生物活性脂质列表。本文综述了已知的氧化脂质、它们在血小板中的活性以及靶向氧化脂质信号的当前治疗方法。
