Lipoxidation in cardiovascular diseases

Abstract

Lipids can go through lipid peroxidation, an endogenous chain reaction that consists in the oxidative degradation of lipids leading to the generation of a wide variety of highly reactive carbonyl species (RCS), such as short-chain carbonyl derivatives and oxidized truncated phospholipids. RCS exert a wide range of biological effects due to their ability to interact and covalently bind to nucleophilic groups on other macromolecules, such as nucleic acids, phospholipids, and proteins, forming reversible and/or irreversible modifications and generating the so-called advanced lipoxidation end-products (ALEs).Lipoxidation plays a relevant role in the onset of cardiovascular diseases (CVD), mainly in the atherosclerosis-based diseases in which oxidized lipids and their adducts have been extensively characterized and associated with several processes responsible for the onset and development of atherosclerosis, such as endothelial dysfunction and inflammation.Herein we will review the current knowledge on the sources of lipids that undergo oxidation in the context of cardiovascular diseases, both from the bloodstream and tissues, and the methods for detection, characterization, and quantitation of their oxidative products and protein adducts.Moreover, lipoxidation and ALEs have been associated with many oxidative-based diseases, including CVD, not only as potential biomarkers but also as therapeutic targets. Indeed, several therapeutic strategies, acting at different levels of the ALEs cascade, have been proposed, essentially blocking ALEs formation, but also their catabolism or the resulting biological responses they induce. However, a deeper understanding of the mechanisms of formation and targets of ALEs could expand the available therapeutic strategies.

Pathological Roles of Mitochondrial Oxidative Stress and Mitochondrial Dynamics in Cardiac Microvascular Ischemia/Reperfusion Injury

“…Increased influx of mitochondrial iron stimulates the formation of more potent and deleterious hydroxyl radical groups from hydrogen peroxide [94,95]. Although the continuous release of ROS from mitochondria during normal conditions appears to play a necessary role in the maintenance of basal cellular function, transiently elevated ROS levels can promote selective protein synthesis, preconditioning, and changes in vascular tone [96,97]. However, even modest, acutely elevated mitochondrial ROS production can lead to cellular dysfunction.…”

Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways

“…Membrane lipids are rich in polyunsaturated fatty acids, which are susceptible to oxidation and peroxidation by hydroxyl ( • OH), hydroperoxyl ( • OOH) radicals, and ROS to generate lipid peroxidation end products, mildly oxidized and truncated oxidized phospholipids [308]. Lipids can also be oxidized by LPs, COXs, and cytochrome P450 to yield lipid peroxidation products, and oxidized phospholipids.…”

Platelets in Healthy and Disease States: From Biomarkers Discovery to Drug Targets Identification by Proteomics

“…Despite reactive oxygen species, originating from platelets or other vascular sources, to regulate normal platelet activation and aggregation, additional oxidative stress in certain settings may be prothrombotic, while reactive nitrogen species have been shown to inhibit platelet function [ 201 ]. An excess of oxidative stress can alter protein structure and function as the result of protein carbonylation through direct oxidation of specific amino acids or formation of specific protein adducts with lipid peroxidation products, such as α,β-unsaturated aldehydes (i.e., 4-hydroxynonenal, 4-HNE) [ 202 ]. Indeed, increased carbonylation of platelet proteins occurs in the presence of exogenous oxidative stress, thrombin stimulation and progression of ageing and diabetes [ 203 ].…”