Brandes Ralf P, Schröder Katrin
Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe-Universität, D-60596 Frankfurt am Main, Germany.
Trends Cardiovasc Med. 2008 Jan;18(1):15-9. doi: 10.1016/j.tcm.2007.11.001.
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are important sources of reactive oxygen species (ROS) and are expressed in at least three different homologues in the vasculature. The enzymes consist of a membrane complex of one of the large catalytically active Nox proteins and p22phox and different cytosolic subunits. Reactive oxygen species formation by the nicotinamide adenine dinucleotide phosphate oxidases Nox1 and Nox2 in arteries is a consequence of an activation of the enzymes by different stimuli such as growth factors, cytokines, and cardiovascular risk factors (cigarette smoke, high blood pressure, oxidized lipids). Nox4, in contrast, is constitutively active, and therefore, ROS formation by this enzyme is controlled on the expression level of the protein. The negative vascular effects of ROS, such as endothelial dysfunction, vascular hypertrophy, aneurysm formation, and inflammatory activation, appear to be the consequence of an activation of Nox1 and Nox2. Nox4, in contrast, potentially elicits positive effects because it promotes differentiation and reduces proliferation of cells. Consequently, selective pharmacologic inhibition of Nox proteins has a potential to interfere with cardiovascular disease initiation and progression.
烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶是活性氧（ROS）的重要来源，在脉管系统中至少以三种不同的同系物形式表达。这些酶由一种具有催化活性的大型Nox蛋白、p22phox和不同的胞质亚基组成的膜复合物构成。动脉中烟酰胺腺嘌呤二核苷酸磷酸氧化酶Nox1和Nox2产生活性氧是不同刺激（如生长因子、细胞因子和心血管危险因素，如香烟烟雾、高血压、氧化脂质）激活这些酶的结果。相比之下，Nox4是组成性激活的，因此，该酶产生的活性氧是在蛋白质表达水平上受到控制的。活性氧的负面血管效应，如内皮功能障碍、血管肥大、动脉瘤形成和炎症激活，似乎是Nox1和Nox2激活的结果。相比之下，Nox4可能产生积极作用，因为它促进细胞分化并减少细胞增殖。因此，对Nox蛋白的选择性药理抑制有可能干扰心血管疾病的发生和发展。
