Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets

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Abstract

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.

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Author and article information

Contributors

Dao Wen Wang: dwwang@tjh.tjmu.edu.cn

Journal

Journal ID (nlm-ta): Signal Transduct Target Ther

Journal ID (iso-abbrev): Signal Transduct Target Ther

Title: Signal Transduction and Targeted Therapy

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 2095-9907

ISSN (Electronic): 2059-3635

Publication date (Electronic): 26 February 2021

Publication date PMC-release: 26 February 2021

Publication date Collection: 2021

Volume: 6

Electronic Location Identifier: 94

Affiliations

[1 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Division of Cardiology, Department of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; Wuhan, China

[2 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, , Huazhong University of Science and Technology, Hubei Province, ; Wuhan, China

[3 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, , Huazhong University of Science and Technology, Hubei, ; Wuhan, China

[4 ]GRID grid.7839.5, ISNI 0000 0004 1936 9721, Institute for Vascular Signalling, Centre for Molecular Medicine, , Goethe University, ; Frankfurt am Main, Germany

Author information

Chen Chen http://orcid.org/0000-0001-5080-9383

Article

Publisher ID: 443

DOI: 10.1038/s41392-020-00443-w

PMC ID: 7910446

PubMed ID: 33637672

SO-VID: f8cfe3d6-bf63-4fc3-82fc-ed98715092f2

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 1 July 2020

Date revision received : 4 October 2020

Date accepted : 15 October 2020

Funding

Funded by: This work was supported in part by National Nature Science Foundation of China (No. 81790624)

Funded by: This work was supported in part by National Nature Science Foundation of China (No. 81700333)

Funded by: This work was supported in part by National Nature Science Foundation of China (No. 81900363)

Funded by: This work was supported in part by National Nature Science Foundation of China (No.81900244)

Funded by: FundRef https://doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft (German Research Foundation);

Award ID: SFB 1039/A6 (to I.F.)

Award Recipient : Ingrid Fleming

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Keywords: cancer,cardiovascular diseases

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Keywords: cancer, cardiovascular diseases

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Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets

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Cancer Metabolism

Most cited references 543

Cancer statistics, 2019

Understanding the tumor immune microenvironment (TIME) for effective therapy

Immunity, inflammation, and cancer.

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