Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain; CIBERCV, Instituto Salud Carlos III, Madrid, Spain.
Cardiovascular Research Chair Autonomous University of Barcelona (UAB), Barcelona, Spain.
Cardiovasc Res. 2021 Jul 27;117(9):2001-2015. doi: 10.1093/cvr/cvab003.
Arachidonic acid is one of the most abundant and ubiquitous ω-6 polyunsaturated fatty acid, present in esterified form in the membrane phospholipids of all mammalian cells and released from phospholipids by several phospholipases in response to various activating or inhibitory stimuli. Arachidonic acid is the precursor of a large number of enzymatically and non-enzymatically derived, biologically active autacoids, including prostaglandins (PGs), thromboxane (TX) A2, leukotrienes, and epoxyeicosatetraenoic acids (collectively called eicosanoids), endocannabinoids and isoprostanes, respectively. Eicosanoids are local modulators of the physiological functions and pathophysiological roles of blood vessels and platelets. For example, the importance of cyclooxygenase (COX)-1-derived TXA2 from activated platelets in contributing to primary haemostasis and atherothrombosis is demonstrated in animal and human models by the bleeding complications and cardioprotective effects associated with low-dose aspirin, a selective inhibitor of platelet COX-1. The relevance of vascular COX-2-derived prostacyclin (PGI2) in endothelial thromboresistance and atheroprotection is clearly shown by animal and human models and by the adverse cardiovascular effects exerted by COX-2 inhibitors in humans. A vast array of arachidonic acid-transforming enzymes, downstream synthases and isomerases, transmembrane receptors, and specificity in their tissue expression make arachidonic acid metabolism a fine-tuning system of vascular health and disease. Its pharmacological regulation is central in human cardiovascular diseases, as demonstrated by biochemical measurements and intervention trials.
花生四烯酸是最丰富和普遍存在的ω-6 多不饱和脂肪酸之一，以酯化形式存在于所有哺乳动物细胞的膜磷脂中，并通过几种磷脂酶在各种激活或抑制刺激下从磷脂中释放。花生四烯酸是大量酶和非酶衍生的、具有生物活性的自体活性物质的前体，包括前列腺素（PGs）、血栓烷（TX）A2、白三烯和环氧二十碳四烯酸（统称为类二十烷酸）、内源性大麻素和异前列腺素。类二十烷酸是血管和血小板生理功能和病理生理作用的局部调节剂。例如，在动物和人类模型中，激活血小板中 COX-1 衍生的 TXA2 在原发性止血和动脉血栓形成中的重要性通过低剂量阿司匹林（血小板 COX-1 的选择性抑制剂）相关的出血并发症和心脏保护作用得到证明。血管 COX-2 衍生的前列环素（PGI2）在血管内皮血栓抵抗力和动脉保护中的相关性通过动物和人类模型以及 COX-2 抑制剂在人类中产生的不良心血管作用得到明确显示。大量的花生四烯酸转化酶、下游合酶和异构酶、跨膜受体以及其组织表达的特异性使花生四烯酸代谢成为血管健康和疾病的精细调节系统。其药理学调节在人类心血管疾病中至关重要，如生化测量和干预试验所示。
