Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Perioperative Inflammation and Infection Group, Department of Medicine, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany.
Eur J Heart Fail. 2019 Apr;21(4):425-435. doi: 10.1002/ejhf.1320. Epub 2018 Oct 19.
Advances in cardiovascular research have identified oxidative stress as an important pathophysiological pathway in the development and progression of heart failure. Oxidative stress is defined as the imbalance between the production of reactive oxygen species (ROS) and the endogenous antioxidant defence system. Under physiological conditions, small quantities of ROS are produced intracellularly, which function in cell signalling, and can be readily reduced by the antioxidant defence system. However, under pathophysiological conditions, the production of ROS exceeds the buffering capacity of the antioxidant defence system, resulting in cell damage and death. Over the last decades several studies have tried to target oxidative stress with the aim to improve outcome in patients with heart failure, with very limited success. The reasons as to why these studies failed to demonstrate any beneficial effects remain unclear. However, one plausible explanation might be that currently employed strategies, which target oxidative stress by exogenous inhibition of ROS production or supplementation of exogenous antioxidants, are not effective enough, while bolstering the endogenous antioxidant capacity might be a far more potent avenue for therapeutic intervention. In this review, we provide an overview of oxidative stress in the pathophysiology of heart failure and the strategies utilized to date to target this pathway. We provide novel insights into modulation of endogenous antioxidants, which may lead to novel therapeutic strategies to improve outcome in patients with heart failure.
心血管研究的进展表明，氧化应激是心力衰竭发生和发展的一个重要病理生理途径。氧化应激是指活性氧（ROS）的产生与内源性抗氧化防御系统之间的失衡。在生理条件下，细胞内会产生少量 ROS，这些 ROS 参与细胞信号转导，并可被抗氧化防御系统迅速还原。然而，在病理生理条件下，ROS 的产生超过了抗氧化防御系统的缓冲能力，导致细胞损伤和死亡。在过去的几十年中，已有多项研究试图通过靶向氧化应激来改善心力衰竭患者的预后，但收效甚微。这些研究未能显示出任何有益效果的原因尚不清楚。然而，一个合理的解释可能是，目前通过外源抑制 ROS 产生或补充外源性抗氧化剂来靶向氧化应激的策略效果不够理想，而增强内源性抗氧化能力可能是一种更有效的治疗干预途径。在这篇综述中，我们概述了氧化应激在心力衰竭病理生理学中的作用以及迄今为止用于靶向该途径的策略。我们提供了对内源性抗氧化剂调节的新见解，这可能为改善心力衰竭患者的预后提供新的治疗策略。
