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Review
. 2025 Dec;39(6):1549-1565.
doi: 10.1007/s10557-024-07655-0. Epub 2024 Dec 9.

Cytochrome P450-derived Epoxyeicosatrienoic Acid, the Regulation of Cardiovascular-related Diseases, and the Implication for Pulmonary Hypertension

Run Lan #  1 , Meng-Jie Zhang #  1 , Ke Liu #  1 , Fang-Fang Meng  1 , Xiao-He Xu  1 , Chen-Chen Wang  1 , Meng-Qi Zhang  1 , Yi Yan #  2 , Jie-Jian Kou  3 , Lu-Ling Zhao  4 , Yang-Yang He  5 , Hong-Da Zhang  6
Affiliations
Review

Cytochrome P450-derived Epoxyeicosatrienoic Acid, the Regulation of Cardiovascular-related Diseases, and the Implication for Pulmonary Hypertension

Run Lan et al. Cardiovasc Drugs Ther. 2025 Dec.

Abstract

Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid (AA) into biologically active epoxyeicosatrienoic acids (EETs), forming a pivotal metabolic pathway (AA-CYP-EETs-soluble epoxide hydrolase-dihydroxyeicosatrienoic acids) implicated in the progression of various disorders. Inflammation is a key contributor to the onset and progression of numerous systemic diseases, and EETs play a significant role in mitigating inflammation. Extensive research highlights the cardiovascular protective effects of EETs, which include vasodilation, anti-hypertensive, and anti-atherosclerotic properties. Interestingly, the relatively less-explored third metabolic pathway of AA exhibits both pro-proliferative and anti-apoptotic effects in endothelial cells and smooth muscle cells. Recent studies have shown elevated levels of EETs catalyzed by CYP epoxygenases in human tumors, promoting tumor progression and metastasis-phenomena closely related to the disease progression in pulmonary hypertension (PH). This review explores the current understanding of the regulatory functions of CYP-derived EETs in cardiovascular diseases and seeks to elucidate their potential implications in PH. Ultimately, understanding the multifaceted roles of EETs may help identify novel therapeutic targets for both cardiovascular diseases and PH.

Keywords: Cardiovascular diseases; Epoxyeicosatrienoic acids; Inflammation; Pulmonary arterial hypertension; Soluble epoxide hydrolase.

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Conflict of interest statement

Declarations. Ethical Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Conflicts of Interest: The authors declare that they have no conflicts of interest.

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