Cardiovascular Division, King's College London British Heart Foundation Centre, London, SE5 9PJ, UK.
Heart Fail Rev. 2011 Jan;16(1):5-12. doi: 10.1007/s10741-010-9186-2.
A heart under chronic stress undergoes cardiac remodelling, a process that comprises structural and functional changes including cardiomyocyte hypertrophy, interstitial fibrosis, contractile dysfunction, cell death and ventricular dilatation. Reactive oxygen species (ROS)-dependent modulation of intracellular signalling is implicated in the development of cardiac remodelling. Among the different ROS sources that are present in the heart, NADPH oxidases (NOXs) are particularly important in redox signalling. NOX isoforms are expressed in multiple cell types including cardiomyocytes, fibroblasts, endothelial cells and inflammatory cells-with the two main isoforms expressed in the heart being NOX2 and NOX4. Recent studies indicate that NOX-dependent signalling is involved in the development of cardiomyocyte hypertrophy, interstitial fibrosis and post-MI remodelling. NOXs may also be involved in the genesis of contractile dysfunction and myocyte apoptosis. Here, we review the main effects of NOXs in the pathogenesis of cardiac remodelling and the redox-sensitive signalling pathways that underlie these effects. The elucidation of mechanisms involved in NOX-dependent regulation of cardiac remodelling may lead to new therapeutic targets for heart failure.
在慢性应激下，心脏会经历心肌重构，这是一个包括结构和功能变化的过程，包括心肌细胞肥大、间质纤维化、收缩功能障碍、细胞死亡和心室扩张。活性氧（ROS）依赖的细胞内信号转导调节与心肌重构的发展有关。在心脏中存在的不同 ROS 来源中，NADPH 氧化酶（NOXs）在氧化还原信号中尤为重要。NOX 同工型在多种细胞类型中表达，包括心肌细胞、成纤维细胞、内皮细胞和炎症细胞-在心脏中表达的两种主要同工型是 NOX2 和 NOX4。最近的研究表明，NOX 依赖性信号参与了心肌细胞肥大、间质纤维化和心肌梗死后重构的发展。NOX 也可能参与收缩功能障碍和心肌细胞凋亡的发生。在这里，我们综述了 NOX 在心肌重构发病机制中的主要作用以及这些作用所依赖的氧化还原敏感信号通路。阐明 NOX 依赖性调节心脏重构的机制可能为心力衰竭提供新的治疗靶点。
