Role of Oxidative Stress in the Pathogenesis of Atherothrombotic Diseases

Abstract

Oxidative stress is generated by the imbalance between reactive oxygen species (ROS) formation and antioxidant scavenger system’s activity. Increased ROS, such as superoxide anion, hydrogen peroxide, hydroxyl radical and peroxynitrite, likely contribute to the development and complications of atherosclerotic cardiovascular diseases (ASCVD). In genetically modified mouse models of atherosclerosis, the overexpression of ROS-generating enzymes and uncontrolled ROS formation appear to be associated with accelerated atherosclerosis. Conversely, the overexpression of ROS scavenger systems reduces or stabilizes atherosclerotic lesions, depending on the genetic background of the mouse model. In humans, higher levels of circulating biomarkers derived from the oxidation of lipids (8-epi-prostaglandin F2α, and malondialdehyde), as well as proteins (oxidized low-density lipoprotein, nitrotyrosine, protein carbonyls, advanced glycation end-products), are increased in conditions of high cardiovascular risk or overt ASCVD, and some oxidation biomarkers have been reported as independent predictors of ASCVD in large observational cohorts. In animal models, antioxidant supplementation with melatonin, resveratrol, Vitamin E, stevioside, acacetin and n-polyunsaturated fatty acids reduced ROS and attenuated atherosclerotic lesions. However, in humans, evidence from large, placebo-controlled, randomized trials or prospective studies failed to show any athero-protective effect of antioxidant supplementation with different compounds in different CV settings. However, the chronic consumption of diets known to be rich in antioxidant compounds (e.g., Mediterranean and high-fish diet), has shown to reduce ASCVD over decades. Future studies are needed to fill the gap between the data and targets derived from studies in animals and their pathogenetic and therapeutic significance in human ASCVD.

Re-Visiting Antioxidant Therapy in Murine Advanced Atherosclerosis with Brussels Chicory, a Typical Vegetable in Mediterranean Diets

“…Oxidative stress is generally thought to be an important contributing factor in the development and progression of atherosclerosis, raising a rational therapeutic strategy that an antioxidant therapy could protect against atherosclerotic cardiovascular diseases [ 5 ]. Unexpectedly, most, if not all, clinical trials carried out so far have consistently shown that antioxidant vitamin regimens (vitamin E or vitamin A precursor β-carotene) or selenium do not prevent cardiovascular disease events, leading to a prevailing concept that the (dietary) antioxidant therapy is unable to counteract cardiovascular diseases [ 7 , 29 , 30 , 31 , 32 ]. Of note, a number of human observational studies have shown an inverse relationship between the whole food, plant-based dietary pattern rich in antioxidant polyphenols and the incidence of cardiovascular disorders [ 8 , 33 , 34 ].…”

Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways

“…The production of ROS and oxidative stress is thought to be a critical mechanism implicated in AAA formation because these have been shown to promote inflammation, matrix degradation, and apoptosis of VSMCs in AAA formation [ 26 ]. ROS, including hydroxyl radical (•OH), superoxide (O2 − ) along with hydrogen peroxide (H2O2), are the highly reactive chemical molecules derived from oxygen [ 27 ]. Excessive ROS levels implicated in VSMCs dysfunction, DNA damage, and lipid/protein peroxidation may result in cellular injury and death irreversibly [ 28 ].…”

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“…Percutaneous coronary intervention (PCI) has become the most common treatment for atherosclerotic stenosis. However, complications such as inflammation, intimal hyperplasia, and in-stent restenosis remain the leading causes of the failure of PCI treatment. , Drug-eluting stents can release drugs with anticoagulant and anti-inflammatory effects at the lesion, inhibiting the development of these complications . Therefore, the advent of drug-eluting stents is seen as a revolutionary development in interventional therapy.…”