Division of Cardiology, Department of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Hubei Province, Wuhan, China.
Signal Transduct Target Ther. 2021 Feb 26;6(1):94. doi: 10.1038/s41392-020-00443-w.
The arachidonic acid (AA) pathway plays a key role in cardiovascular biology, carcinogenesis, and many inflammatory diseases, such as asthma, arthritis, etc. Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2), which is in turn further metabolized by cyclooxygenases (COXs) and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes to a spectrum of bioactive mediators that includes prostanoids, leukotrienes (LTs), epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid (diHETEs), eicosatetraenoic acids (ETEs), and lipoxins (LXs). Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases (CVD), cancers, and inflammatory diseases. This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2. Thus, we herein present a synopsis of AA metabolism in human health, cardiovascular and cancer biology, and the signaling pathways involved in these processes. To explore the role of the AA metabolism and potential therapies, we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.
花生四烯酸（AA）途径在心血管生物学、致癌作用和许多炎症性疾病中发挥着关键作用，如哮喘、关节炎等。细胞膜内表面的酯化 AA 通过磷脂酶 A2（PLA2）水解为其游离形式，PLA2 进一步被环氧化酶（COXs）和脂氧合酶（LOXs）以及细胞色素 P450（CYP）代谢为一系列生物活性介质，包括前列腺素、白三烯（LTs）、环氧二十碳三烯酸（EETs）、二羟二十碳四烯酸（diHETEs）、二十碳四烯酸（ETEs）和脂氧素（LXs）。其中许多介质被认为是心血管疾病（CVD）、癌症和炎症性疾病的新型预防和治疗靶点。本文旨在总结 AA 代谢途径的生理和病理生理学重要性，并概述与 AA 相关的三条主要代谢途径在 CVD 和癌症进展中的作用的分子机制，为开发 CVD 和抗癌药物（如 EETs 或 2J2 的抑制剂）提供有价值的见解。因此，我们在此概述了 AA 在人类健康、心血管和癌症生物学中的代谢以及这些过程中涉及的信号通路。为了探索 AA 代谢的作用和潜在治疗方法，我们还介绍了目前针对不同疾病状态下 AA 代谢的新临床研究。
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