Lan Run, Zhang Meng-Jie, Liu Ke, Meng Fang-Fang, Xu Xiao-He, Wang Chen-Chen, Zhang Meng-Qi, Yan Yi, Kou Jie-Jian, Zhao Lu-Ling, He Yang-Yang, Zhang Hong-Da
School of Pharmacy, Henan University, Kaifeng, 475004, China.
Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Cardiovasc Drugs Ther. 2024 Dec 9. doi: 10.1007/s10557-024-07655-0.
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.
细胞色素P450（CYP）环氧合酶将花生四烯酸（AA）代谢为具有生物活性的环氧二十碳三烯酸（EETs），形成一条关键的代谢途径（AA-CYP-EETs-可溶性环氧化物水解酶-二羟基二十碳三烯酸），该途径与多种疾病的进展有关。炎症是众多全身性疾病发病和进展的关键因素，而EETs在减轻炎症方面发挥着重要作用。大量研究强调了EETs的心血管保护作用，包括血管舒张、抗高血压和抗动脉粥样硬化特性。有趣的是，相对较少被探索的AA第三条代谢途径在内皮细胞和平滑肌细胞中表现出促增殖和抗凋亡作用。最近的研究表明，人类肿瘤中由CYP环氧合酶催化的EETs水平升高，促进肿瘤进展和转移，这些现象与肺动脉高压（PH）的疾病进展密切相关。本综述探讨了目前对CYP衍生的EETs在心血管疾病中的调节功能的理解，并试图阐明它们在PH中的潜在影响。最终，了解EETs的多方面作用可能有助于确定心血管疾病和PH的新型治疗靶点。
