Roles of Vascular Oxidative Stress and Nitric Oxide in the Pathogenesis of Atherosclerosis
2017/02/16 by Ulrich Förstermann, Ning Xia, Huige Li · 1,474 citations
Chemistry · Immunology and Microbiology · Medicine · #Biochemistry #Biology #Cardiovascular, Neuropeptides, and Oxidative Stress Research #Chemistry #Diabetes mellitus #Endocrinology #Endothelial dysfunction #Endothelium #Enzyme #Internal medicine #Medicine #NADPH oxidase #Neutrophil, Myeloperoxidase and Oxidative Mechanisms #Nicotinamide adenine dinucleotide phosphate #Nitric Oxide and Endothelin Effects #Nitric oxide #Oxidase test #Oxidative stress #Reactive nitrogen species #Reactive oxygen species #Xanthine oxidase
paper · doi:10.1161/circresaha.116.309326
published in Circulation Research 120(4), 713-735 (Lippincott Williams & Wilkins)
openalex publication_date 2017/02/16 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04
Abstract
Major reactive oxygen species (ROS)-producing systems in vascular wall include NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase, xanthine oxidase, the mitochondrial electron transport chain, and uncoupled endothelial nitric oxide (NO) synthase. ROS at moderate concentrations have important signaling roles under physiological conditions. Excessive or sustained ROS production, however, when exceeding the available antioxidant defense systems, leads to oxidative stress. Animal studies have provided compelling evidence demonstrating the roles of vascular oxidative stress and NO in atherosclerosis. All established cardiovascular risk factors such as hypercholesterolemia, hypertension, diabetes mellitus, and smoking enhance ROS generation and decrease endothelial NO production. Key molecular events in atherogenesis such as oxidative modification of lipoproteins and phospholipids, endothelial cell activation, and macrophage infiltration/activation are facilitated by vascular oxidative stress and inhibited by endothelial NO. Atherosclerosis develops preferentially in vascular regions with disturbed blood flow (arches, branches, and bifurcations). The fact that these sites are associated with enhanced oxidative stress and reduced endothelial NO production is a further indication for the roles of ROS and NO in atherosclerosis. Therefore, prevention of vascular oxidative stress and improvement of endothelial NO production represent reasonable therapeutic strategies in addition to the treatment of established risk factors (hypercholesterolemia, hypertension, and diabetes mellitus).
Citations
Cited by
- Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Men and Women With Major Depressive Disorder
- Amelioration of endothelial dysfunction by sodium glucose co‐transporter 2 inhibitors: pieces of the puzzle explaining their cardiovascular protection
- SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits
- ESC Working Group on Coronary Pathophysiology and Microcirculation position paper on ‘coronary microvascular dysfunction in cardiovascular disease’
- Downregulation of G3BP2 reduces atherosclerotic lesions in ApoE mice
- Dairy bioactive proteins and peptides: a narrative review
- Repurposing drugs to fight aging: The difficult path from bench to bedside
- Lipid metabolic alterations in cancer: Common pathophysiology with cardiovascular disease
- Inhibition of ferroptosis underlies EGCG mediated protection against Parkinson’s disease in a Drosophila model
- NADP+/NADPH in Metabolism and its Relation to Cardiovascular Pathologies
- Current landscape and future directions of drug-eluting balloons in cardiovascular interventions
- Retinal microvascular alterations consistent with endothelial dysregulation in paediatric post-COVID-19 syndrome: A prospective matched-cohort study
- Innate immune receptors in platelets and platelet-leukocyte interactions
- Pathophysiology of Atherosclerosis
- Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets
- Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies. [europepmc]
- Loneliness, Social Isolation, and Cardiovascular Health. [europepmc]
- Polyphenols and Oxidative Stress in Atherosclerosis-Related Ischemic Heart Disease and Stroke. [europepmc]
- New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis. [europepmc]
- Vascular Oxidative Stress: Impact and Therapeutic Approaches. [europepmc]
- Targeting Early Atherosclerosis: A Focus on Oxidative Stress and Inflammation. [europepmc]
- Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS? [europepmc]
- Polycystic ovary syndrome and mitochondrial dysfunction. [europepmc]
- NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets. [europepmc]
- ESC Working Group on Coronary Pathophysiology and Microcirculation position paper on 'coronary microvascular dysfunction in cardiovascular disease'. [europepmc]
- The Role of Oxidative Stress in Cardiac Disease: From Physiological Response to Injury Factor. [europepmc]
- Effects of tobacco cigarettes, e-cigarettes, and waterpipe smoking on endothelial function and clinical outcomes. [europepmc]
- Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia. [europepmc]
- Protective Effects of Estrogen on Cardiovascular Disease Mediated by Oxidative Stress. [europepmc]
- Reactive oxygen species-based nanomaterials for the treatment of myocardial ischemia reperfusion injuries. [europepmc]
- Pathophysiology of Atherosclerosis. [europepmc]
- Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation. [europepmc]
- ROS: Basic Concepts, Sources, Cellular Signaling, and its Implications in Aging Pathways. [europepmc]
- ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis. [europepmc]
- Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes. [europepmc]
- Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections. [europepmc]
- The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction. [europepmc]
- Oxidative stress in the eye and its role in the pathophysiology of ocular diseases. [europepmc]
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets. [europepmc]
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases. [europepmc]
Related