Antioxidants in the Fight Against Atherosclerosis: Is This a Dead End?

Abstract

Purpose of ReviewThe purpose of this review is to focus on the outcome of recent antioxidant interventions using synthetic and naturally occurring molecules established as adjuvant strategies to lipid-lowering or anti-inflammatory therapies designed to reduce the risk of cardiovascular disease.Recent FindingsTo date, accumulated evidence regarding oxidation as a pro-atherogenic factor indicates that redox biochemical events involved in atherogenesis are indeed a very attractive target for the management of cardiovascular disease in the clinic. Nevertheless, although evidence indicates that redox reactions are important in the initiation and progression of atherosclerosis, oxidation with a pro-atherogenic context does not eliminate the fact that oxidation participates in many cases as an essential messenger of important cellular signaling pathways. Therefore, disease management and therapeutic goals require not only high-precision and high-sensitivity methods to detect in plasma very low amounts of reducing and oxidizing molecules but also a much better understanding of the normal processes and metabolic pathways influenced and/or controlled by oxidative stress. As several methodologies have been specifically described for the quantification of the total antioxidant capacity and the oxidation state of diverse biological systems, a successful way to carefully study how redox reactions influence atherosclerosis can be achieved.SummarySince there is still a lack of standardization with many of these methods, clinical trials studying antioxidant capacity have been difficult to compare and therefore difficult to use in order to reach a conclusion. We believe a comprehensive analysis of new knowledge and its relationship with the presence of plasma antioxidants and their reducing capacity will undoubtedly open new ways to understand and develop new therapeutic pathways in the fight not only against atherosclerosis but also against other degenerative diseases.

Overview of OxLDL and Its Impact on Cardiovascular Health: Focus on Atherosclerosis

“…Overproduction of oxLDL triggers the LOX-1 expression in VSMCs and also triggers apoptosis ( Wu et al, 2017 ). Expression of the proapoptotic protein Bcl-2-associated X protein (Bax) is increased, as well as the expression of the anti-apoptotic protein Bcl2 in response to excessive oxLDL formation ( Liu et al, 2005 ; Toledo-Ibelles and Mas-Oliva, 2018 ). LOX-1 mediates this effect, and, accordingly, anti-LOX-1 antibodies inhibit the ox-LDL-induced apoptosis.…”

Vascular Macrophages in Atherosclerosis

“…Antioxidant therapy such as febuxostat, an inhibitor of xanthine oxidase, also functions partly through effects on macrophages [140]. Antioxidant therapy could modify the process of atherogenesis by preventing oxidation of LDL, formation of ROS, and subsequent release of inflammatory cytokines in macrophages [141]. Clinical trials targeting other molecules, including CX3CR1, IL-12, LXR, IRF5, and PPAR- γ , are still on the way and have not reached any conclusion.…”

Novel Phytoconstituents of an Aqueous Pod Extract of Prosopis Cineraria (L.) Druce Attenuate Atherosclerotic Plaque and Hypercholesterolemia in Rabbits

“…Several herbal formulations have been reported in the literature for the treatment of hypercholesterolemia and diabetes that were used historically by local populations of people based on traditional knowledge passed down from generation to generation [4][5][6][7]. Dietary supplements of antioxidant formulations are also available to ameliorate risk factors associated with hypercholesterolemia [8][9][10]. Several studies have indicated that the use of plant-derived antioxidant formulations are more preferred than synthetic drugs to reduce oxidative injury [11].…”