Department of Nutrition, Food & Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA.
Institute of Sports Sciences and Medicine, College of Human Sciences, Florida State University, Tallahassee, FL 32306, USA.
Int J Mol Sci. 2019 Aug 2;20(15):3775. doi: 10.3390/ijms20153775.
NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.
NADPH 氧化酶（NOX）是酶复合物，作为血管功能障碍发展的关键分子受到广泛关注。NOX 的主要功能是生成活性氧（ROS），被认为是内皮细胞中 ROS 产生的主要来源。内皮是一层薄的单层细胞，排列在血管的内表面，作为一个分泌器官，维持血流的动态平衡。内皮型一氧化氮合酶（eNOS）的酶促产生一氧化氮（NO）对于介导内皮功能至关重要，氧化应激可导致 eNOS 失调和内皮功能障碍。胰岛素是增加血流和内皮依赖性血管舒张的刺激物。然而，心血管疾病和 2 型糖尿病的特点是内皮细胞氧化还原环境的控制不佳，NOX 产生的 ROS 过度产生。2 型糖尿病模型的研究表明，异常的 NOX 激活导致 eNOS 解偶联和内皮功能障碍。众所周知，内皮功能障碍先于心血管疾病的发生，因此，NOX 是 2 型糖尿病与血管并发症之间的重要分子联系。本综述的目的是描述内皮功能正常、健康的生理机制，并强调在葡萄糖稳态受损时，NOX 在介导内皮功能障碍方面的核心作用。
