Oxidative Stress in Human Atherothrombosis: Sources, Markers and Therapeutic Targets

Abstract

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.

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK)/Fibroblast Growth Factor-Inducible 14 (Fn14) Axis in Cardiovascular Diseases: Progress and Challenges

“…Oxidative stress is also associated with inflammation and the development of atherosclerosis [68]. The increase in reactive oxygen species (ROS) production is produced in part by the activation of NADPH oxidases [69].…”

Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects

“…Numerous studies showed that the AGEs and the advanced lipoxidation end products (ALEs) are involved in the development and progression of chronic degenerative diseases, including diabetes [28][29][30], cardiovascular diseases [29,31,32], neurological disorder [33,34], some types of cancer [35,36], and all those pathologies in which the mechanisms of oxidative stress are involved, as well as the senescence processes [33].…”

Thrombogenic and Inflammatory Reactions to Biomaterials in Medical Devices

“…Atherothrombosis is a complex and abnormal chronic inflammatory/immune arterial wall remodeling initiated by the deposition of lipids and oxidative stress followed by recruitment of circulating leukocytes, proliferative responses with atheromatous plaque growth, proteolysis, neo-angiogenesis, apoptosis, calcification, fibrosis, plaque rupture, and thrombosis (Martin-Ventura et al, 2017). While platelets play a central role in arterial thrombogenesis because of fast flow conditions, a thrombus developing on disrupted plaques regularly involves great quantities of fibrin (Figure 1).…”