British Heart Foundation Centre of Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, United Kingdom.
Antioxid Redox Signal. 2023 Feb;38(4-6):371-387. doi: 10.1089/ars.2022.0176.
Reactive oxygen species (ROS) play a key role in the pathogenesis of cardiac remodeling and the subsequent progression to heart failure (HF). Nicotinamide adenosine dinucleotide phosphate (NADPH) oxidases (NOXs) are one of the major sources of ROS and are expressed in different heart cell types, including cardiomyocytes, endothelial cells, fibroblasts, and inflammatory cells. NOX-derived ROS are usually produced in a regulated and spatially confined fashion and typically linked to specific signaling. The two main cardiac isoforms, namely nicotinamide adenine dinucleotide phosphate oxidase isoform 2 (NOX2) and nicotinamide adenine dinucleotide phosphate oxidase isoform 4 (NOX4), possess different biochemical and (patho)physiological properties and exert distinct effects on the cardiac phenotype in many settings. Recent work has defined important cell-specific effects of NOX2 that contribute to pathological cardiac remodeling and dysfunction. NOX4, on the other hand, may exert protective effects by stimulating adaptive stress responses, with recent data showing that NOX4-mediated signaling regulates transcription and metabolism in the heart. The inhibition of NOX2 appears to be a very promising therapeutic target to ameliorate pathological cardiac remodeling. If the beneficial effects of NOX4 can be enhanced, this might be a unique approach to boosting adaptive responses and thereby impact cell survival, activation, contractility, and growth. Increasing knowledge regarding the intricacies of NOX-mediated signaling may yield tractable therapeutic targets, in contrast to the non-specific targeting of oxidative stress. 38, 371-387.
活性氧（ROS）在心脏重构的发病机制及其随后进展为心力衰竭（HF）中起着关键作用。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOXs）是 ROS 的主要来源之一，存在于不同的心脏细胞类型中，包括心肌细胞、内皮细胞、成纤维细胞和炎症细胞。NOX 衍生的 ROS 通常以受调控和空间限制的方式产生，并且通常与特定信号相关联。两种主要的心脏同工型，即烟酰胺腺嘌呤二核苷酸磷酸氧化酶同工型 2（NOX2）和烟酰胺腺嘌呤二核苷酸磷酸氧化酶同工型 4（NOX4），具有不同的生化和（病理）生理特性，并在许多情况下对心脏表型产生不同的影响。最近的研究定义了 NOX2 的重要细胞特异性效应，这些效应有助于病理性心脏重构和功能障碍。另一方面，NOX4 通过刺激适应性应激反应可能发挥保护作用，最近的数据表明，NOX4 介导的信号调节心脏中的转录和代谢。抑制 NOX2 似乎是改善病理性心脏重构的很有前途的治疗靶点。如果能够增强 NOX4 的有益作用，这可能是一种独特的方法，可以增强适应性反应，从而影响细胞存活、激活、收缩性和生长。对 NOX 介导的信号的复杂性的深入了解可能会产生可治疗的靶点，而不是非特异性靶向氧化应激。38，371-387。
