ElKhatib Mohammed A W, Isse Fadumo Ahmed, El-Kadi Ayman O S
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Drug Metab Rev. 2023 Feb-May;55(1-2):50-74. doi: 10.1080/03602532.2022.2162075. Epub 2022 Dec 27.
The incidence of heart failure (HF) is generally preceded by cardiac hypertrophy (CH), which is the enlargement of cardiac myocytes in response to stress. During CH, the metabolism of arachidonic acid (AA), which is present in the cell membrane phospholipids, is modulated. Metabolism of AA gives rise to hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) cytochrome P450 (CYP) ω-hydroxylases and CYP epoxygenases, respectively. A plethora of studies demonstrated the involvement of CYP-mediated AA metabolites in the pathogenesis of CH. Also, inflammation is known to be a characteristic hallmark of CH. In this review, our aim is to highlight the impact of inflammation on CYP-derived AA metabolites and CH. Inflammation is shown to modulate the expression of various CYP ω-hydroxylases and CYP epoxygenases and their respective metabolites in the heart. In general, HETEs such as 20-HETE and mid-chain HETEs are pro-inflammatory, while EETs are characterized by their anti-inflammatory and cardioprotective properties. Several mechanisms are implicated in inflammation-induced CH, including the modulation of NF-κB and MAPK. This review demonstrated the inflammatory modulation of cardiac CYPs and their metabolites in the context of CH and the anti-inflammatory strategies that can be employed in the treatment of CH and HF.
心力衰竭（HF）的发生通常先于心肌肥大（CH），心肌肥大是心肌细胞因应激而增大。在CH过程中，细胞膜磷脂中存在的花生四烯酸（AA）的代谢受到调节。AA的代谢分别通过细胞色素P450（CYP）ω-羟化酶和CYP环氧化酶产生羟基二十碳四烯酸（HETEs）和环氧二十碳三烯酸（EETs）。大量研究表明CYP介导的AA代谢产物参与了CH的发病机制。此外，炎症是CH的一个典型特征。在本综述中，我们的目的是强调炎症对CYP衍生的AA代谢产物和CH的影响。炎症被证明可调节心脏中各种CYP ω-羟化酶和CYP环氧化酶及其各自代谢产物的表达。一般来说，诸如20-HETE和中链HETEs等HETEs具有促炎作用，而EETs则具有抗炎和心脏保护特性。炎症诱导CH涉及多种机制，包括对NF-κB和MAPK的调节。本综述阐述了在CH背景下心脏CYP及其代谢产物的炎症调节以及可用于治疗CH和HF的抗炎策略。
