Oxidative Stress and Antioxidants in Atherosclerosis Development and Treatment

Abstract

Atherosclerosis can be regarded as chronic inflammatory disease affecting the arterial wall. Despite the recent progress in studying the pathogenesis of atherosclerosis, some of the pathogenic mechanisms remain to be fully understood. Among these mechanisms is oxidative stress, which is closely linked to foam cells formation and other key events in atherosclerosis development. Two groups of enzymes are involved in the emergence of oxidative stress: Pro-oxidant (including NADPH oxidases, xanthine oxidases, and endothelial nitric oxide synthase) and antioxidant (such as superoxide dismutase, catalases, and thioredoxins). Pro-oxidant enzymes in normal conditions produce moderate concentrations of reactive oxidant species that play an important role in cell functioning and can be fully utilized by antioxidant enzymes. Under pathological conditions, activities of both pro-oxidant and antioxidant enzymes can be modified by numerous factors that can be relevant for developing novel therapies. Recent studies have explored potential therapeutic properties of antioxidant molecules that are capable to eliminate oxidative damage. However, the results of these studies remain controversial. Other perspective approach is to inhibit the activity of pro-oxidant enzymes and thus to slow down the progression of atherosclerosis. In this review we summarized the current knowledge on oxidative stress in atherosclerosis and potential antioxidant approaches. We discuss several important antioxidant molecules of plant origin that appear to be promising for treatment of atherosclerosis.

Risk assessment of cardiotoxicity to zebrafish (Danio rerio) by environmental exposure to triclosan and its derivatives

“…SOD is the first line of antioxidant defense system. Under the low concentration of TCS-DT exposure, the SOD activity of heart tissue increases, strengthening the elimination of active oxygen free radicals, so as to avoid the oxidative damage to organism tissues (Li et al, 2012), but they will trigger oxidative stress in the absence of downstream enzymes sufficient to detoxify the final SOD product (Poznyak et al, 2020). Decreased SOD levels are an important indicator of oxidative stress (Akila and Vennila, 2016).…”

Oxidative Stress and New Pathogenetic Mechanisms in Endothelial Dysfunction: Potential Diagnostic Biomarkers and Therapeutic Targets

“…Based on their origins, small molecule antioxidants can be endogenous (e.g., uric acid, coenzyme Q, bilirubin) or exogenous (e.g., vitamins C and E, flavonoid, carotenes). Major antioxidant systems present in the vascular wall include superoxide dismutase, catalase, glutathione peroxidase, thioredoxin, peroxiredoxin [ 73 ]. The dysregulation of oxidant and antioxidant enzymes, such as an inefficient degradation of ROS, an increased activity of oxidant enzymes or a reduced/aberrant activity of antioxidant enzymes, produces an increase in ROS levels which overcome the buffering capacity of ROS scavengers causing oxidative stress [ 74 ].…”

“…Superoxide dismutase (SOD) belongs to a family of enzymes that catalyze the conversion of the O2- to H 2 O 2 [ 3 ]. Three isoforms of SODs have been described: SOD1 is found in the cytoplasm and on the inner mitochondrial membrane; SOD2 is located in the mitochondrial matrix, and SOD3 is extracellular [ 73 ]. In endothelial cells, it has been reported that inhibition of SOD1 increased the steady-state levels of O2- and reduced the phosphorylation of extracellular signal-regulated kinases (ERK) 1/2.…”

“…GPx-1 deficiency has been linked to the development of endothelial dysfunction, inflammation, and neointimal formation [ 77 ]. The role of GPx-1 has been demonstrated in the normalization of VSMC proliferation rate through the inhibition of matrix metalloproteinase 9 (MMP9), and the consequent restoring of the endothelial function [ 73 ]. A more aggressive atherosclerosis has been reported in double knockout (ApoE−/−) (GPx-1−/−) mice compared to (ApoE−/−) controls, with a marked increase in ROS levels and a decrease in NO bioavailability, which was associated with increased protein nitration within the atherosclerotic lesions [ 78 ].…”

“…A pivotal role of Trx has been reported in the regulation of endothelial cell survival, protecting the cells from laminar shear stress, and inhibiting the activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) consequent to tumor necrosis factor alpha (TNF-α) exposure [ 3 ]. Trx was also found in medial smooth muscle cells of coronary arteries of healthy humans, while a diffused expression pattern was evident in atherosclerotic arteries [ 73 ]. The system was also reported to exert an essential role in regulating metabolic processes, insulin signaling, blood pressure regulation, and inflammation [ 73 ].…”