Vascular Research Lab, FIIS-Fundación Jiménez Díaz-Autonoma University, 28040 Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain.
Int J Mol Sci. 2017 Nov 3;18(11):2315. doi: 10.3390/ijms18112315.
Atherothrombosis remains one of the main causes of morbidity and mortality worldwide. The underlying pathology is a chronic pathological vascular remodeling of the arterial wall involving several pathways, including oxidative stress. Cellular and animal studies have provided compelling evidence of the direct role of oxidative stress in atherothrombosis, but such a relationship is not clearly established in humans and, to date, clinical trials on the possible beneficial effects of antioxidant therapy have provided equivocal results. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is one of the main sources of reactive oxygen species (ROS) in human atherothrombosis. Moreover, leukocyte-derived myeloperoxidase (MPO) and red blood cell-derived iron could be involved in the oxidative modification of lipids/lipoproteins (LDL/HDL) in the arterial wall. Interestingly, oxidized lipoproteins, and antioxidants, have been analyzed as potential markers of oxidative stress in the plasma of patients with atherothrombosis. In this review, we will revise sources of ROS, focusing on NADPH oxidase, but also on MPO and iron. We will also discuss the impact of these oxidative systems on LDL and HDL, as well as the value of these modified lipoproteins as circulating markers of oxidative stress in atherothrombosis. We will finish by reviewing some antioxidant systems and compounds as therapeutic strategies to prevent pathological vascular remodeling.
动脉粥样血栓形成仍然是全球发病率和死亡率的主要原因之一。其潜在的病理学改变是动脉壁的慢性病理性血管重塑，涉及多个途径，包括氧化应激。细胞和动物研究为氧化应激在动脉粥样血栓形成中的直接作用提供了令人信服的证据，但这种关系在人类中并不明确，迄今为止，关于抗氧化治疗可能有益效果的临床试验提供了模棱两可的结果。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶是人类动脉粥样血栓形成中活性氧（ROS）的主要来源之一。此外，白细胞衍生的髓过氧化物酶（MPO）和红细胞衍生的铁可能参与动脉壁中脂质/脂蛋白（LDL/HDL）的氧化修饰。有趣的是，氧化脂蛋白和抗氧化剂已被分析为动脉粥样血栓形成患者血浆中氧化应激的潜在标志物。在这篇综述中，我们将回顾 ROS 的来源，重点介绍 NADPH 氧化酶，但也包括 MPO 和铁。我们还将讨论这些氧化系统对 LDL 和 HDL 的影响，以及这些修饰脂蛋白作为动脉粥样血栓形成中循环氧化应激标志物的价值。最后，我们将回顾一些抗氧化系统和化合物作为预防病理性血管重塑的治疗策略。
