ArticlePLoS biology2020
NOX5-induced uncoupling of endothelial NO synthase is a causal mechanism and theragnostic target of an age-related hypertension endotype.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Synergistic Network Pharmacology: Preclinical Validation and Clinical Safety in Acute Ischemic Stroke.Journal of the American Heart Association · 2025Trial
- An Early Value Assessment of Biomarker-Guided Precision Medicine for Treatment-Resistant Hypertension: A Headroom and Threshold Analysis.Applied health economics and health policy · 2026Article
- A crosstalk between tumor cells and adipocytes facilitates tumor cell migration and invasion.International journal of biological sciences · 2026Article
- Oxidative Stress and Inflammation in Uterine-Vascular Adaptation During Pregnancy.Antioxidants (Basel, Switzerland) · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Atherosclerosis in diabetes mellitus: novel mechanisms and mechanism-based therapeutic approaches.Nature reviews. Cardiology · 2025Review
- Diabetes-Driven Atherosclerosis: Updated Mechanistic Insights and Novel Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Reactive oxygen species in hypertension.Nature reviews. Cardiology · 2025Review
- Declining nitric oxide bioavailability in cardiovascular aging: mechanistic insights and emerging interventions.The journal of cardiovascular aging · 2025Article
- Oxidative Stress in Kidney Injury and Hypertension.Antioxidants (Basel, Switzerland) · 2024Review
- NADPH Oxidase 5 (NOX5) Upregulates MMP-10 Production and Cell Migration in Human Endothelial Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Oxidative Stress, Antioxidants and Hypertension.Antioxidants (Basel, Switzerland) · 2023Review
- Impact of endocrine disrupting chemicals and pharmaceuticals on Sertoli cell development and functions.Frontiers in endocrinology · 2023Review
- NOX2 and NOX5 are increased in cardiac microvascular endothelium of deceased COVID-19 patients.International journal of cardiology · 2023Article
- Functional interactions between NADPH oxidase 5 and actin.Frontiers in cell and developmental biology · 2023Article
- Article
- NADPH Oxidases in Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction.Antioxidants (Basel, Switzerland) · 2022Review
- Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology.Cardiovascular research · 2022Review
- Endothelial reactive oxygen-forming NADPH oxidase 5 is a possible player in diabetic aortic aneurysm but not atherosclerosis.Scientific reports · 2022Article
- Nitric-Oxide-Mediated Signaling in Podocyte Pathophysiology.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
17 authors at 9 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypertension is the most important cause of death and disability in the elderly. In 9 out of 10 cases, the molecular cause, however, is unknown. One mechanistic hypothesis involves impaired endothelium-dependent vasodilation through reactive oxygen species (ROS) formation. Indeed, ROS forming NADPH oxidase (Nox) genes associate with hypertension, yet target validation has been negative. We re-investigate this association by molecular network analysis and identify NOX5, not present in rodents, as a sole neighbor to human vasodilatory endothelial nitric oxide (NO) signaling. In hypertensive patients, endothelial microparticles indeed contained higher levels of NOX5-but not NOX1, NOX2, or NOX4-with a bimodal distribution correlating with disease severity. Mechanistically, mice expressing human Nox5 in endothelial cells developed-upon aging-severe systolic hypertension and impaired endothelium-dependent vasodilation due to uncoupled NO synthase (NOS). We conclude that NOX5-induced uncoupling of endothelial NOS is a causal mechanism and theragnostic target of an age-related hypertension endotype. Nox5 knock-in (KI) mice represent the first mechanism-based animal model of hypertension.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.