Urbański Karol, Nowak Michal, Guzik Tomasz J
Postepy Biochem. 2013;59(4):424-31.
The maintenance of blood vessel homeostasis is closely associated with Reactive Oxygen and Nitrogen Species (ROS and RNS) production in the blood vessel wall. The main molecules taking part in this process are nitric oxide (NO), superoxide anion (O2*-), hydrogen peroxide (H2O2) and their derivatives. The production of these factors occurs in health and disease, however the increased ROS release is often referred to as oxidative stress. While initially oxidative stress was considered systemically, recent data indicate that it occurs locally in subcellular spaces and may be a result of dysfunction of individual enzyme systems. Oxidative stress induces inflammation, proliferation and migration of vascular smooth muscle cells, may regulate apoptosis and the function of the cells of vascular wall, finally leading to dysfunction of endothelium, media and adventitia, leading to cardiovascular diseases such as atherosclerosis, hypertension or heart failure. It is believed that a family of NADPH oxidases is the main source of ROS in the vessel wall, but also in other organs and tissues. It consists of seven known and quite precisely characterized homologues (NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2) which often have very distinct activity and cellular localization and function. Besides harmful actions, we are beginning to understand the protective effects of ROS and RNS. They have many functions regulating redox-sensitive gene expression and influencing a proper function of cells and vessels. NOX4 has been particularly well characterized in this respect. Thus, the maintenance of the right homeostasis depends not only on ROS removing capabilities, but especially on preserving the adequate level of ROS production.
血管稳态的维持与血管壁中活性氧和氮物种(ROS和RNS)的产生密切相关。参与这一过程的主要分子是一氧化氮(NO)、超氧阴离子(O2*-)、过氧化氢(H2O2)及其衍生物。这些因子在健康和疾病状态下均会产生,然而ROS释放增加通常被称为氧化应激。虽然最初氧化应激被认为是全身性的,但最近的数据表明它发生在亚细胞空间局部,可能是个体酶系统功能障碍的结果。氧化应激会诱导血管平滑肌细胞的炎症、增殖和迁移,可能调节细胞凋亡和血管壁细胞的功能,最终导致内皮、中膜和外膜功能障碍,引发心血管疾病,如动脉粥样硬化、高血压或心力衰竭。据信,NADPH氧化酶家族是血管壁以及其他器官和组织中ROS的主要来源。它由七个已知且特征相当明确的同源物组成(NOX1、NOX2、NOX3、NOX4、NOX5、DUOX1和DUOX2),它们通常具有非常不同的活性、细胞定位和功能。除了有害作用外我们也开始了解ROS和RNS的保护作用。它们具有许多调节氧化还原敏感基因表达并影响细胞和血管正常功能的功能。在这方面,NOX4的特征尤为明显。因此,维持适当的稳态不仅取决于ROS的清除能力,更取决于保持适当水平的ROS产生。