ArticleRedox biology2019
Increased mitochondrial NADPH oxidase 4 (NOX4) expression in aging is a causative factor in aortic stiffening.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25-57% elevation in risk.GeroScience · 2025Pooled it
- Sex Differences and Oxidative Stress in Cardiovascular Disease.Physiology (Bethesda, Md.) · 2026Review
- Cocoa-Based Plant Matrices in Glucose Metabolism: Bioactive Compounds and Redox Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- Pyrrolizidine Alkaloid-Induced Hepatotoxicity: A Narrative Review on Molecular Mechanisms and Detoxification Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Triple-Marker Screening of 20 Terpenes Identifies Candidate Modulators of Senescence-Associated Phenotypes in D-Galactose-Treated Endothelial Cells.Molecules (Basel, Switzerland) · 2026Article
- Aging-AssociatedJournal of the American Heart Association · 2026Article
- Article
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- Endothelial MerTK impairment accelerates the development of atherosclerosis.Redox biology · 2025Article
- NOX4 Regulates NLRP3 by Inhibiting the Ubiquitination of LRRC8A to Promote Ferroptosis in Nucleus Pulposus Cells.Inflammation · 2025Article
- Anti-ageing interventions for the treatment of cardiovascular disease.Cardiovascular research · 2025Review
- Evaluating the Oxidative Balance Score for Peripheral Artery Disease Risk: Integrating Epidemiologic Modeling and SHAP-Interpretable Machine Learning in NHANES.Food science & nutrition · 2025Article
- Beyond conventional therapy: NOX4 as a promising target in cardiomyopathy.Molecular biology reports · 2025Review
- Age-Associated Increase in Growth Differentiation Factor 15 Levels Correlates With Central Arterial Stiffness and Predicts All-Cause Mortality in a Sardinian Population Cohort.Journal of the American Heart Association · 2025Article
- Mitochondrial Dysfunction: A New Hallmark in Hereditable Thoracic Aortic Aneurysm Development.Cells · 2025Review
- Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise.Journal of cardiovascular translational research · 2025Review
- FNDC5/irisin mitigates the cardiotoxic impacts of cancer chemotherapeutics by modulating ROS-dependent and -independent mechanisms.Redox biology · 2025Article
- Oxidative DNA Damage and Arterial Hypertension in Light of Current ESC Guidelines.International journal of molecular sciences · 2024Review
- Ginsenoside RbChinese herbal medicines · 2024Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Aging is characterized by increased aortic stiffness, an early, independent predictor and cause of cardiovascular disease. Oxidative stress from excess reactive oxygen species (ROS) production increases with age. Mitochondria and NADPH oxidases (NOXs) are two major sources of ROS in cardiovascular system. We showed previously that increased mitochondrial ROS levels over a lifetime induce aortic stiffening in a mouse oxidative stress model. Also, NADPH oxidase 4 (NOX4) expression and ROS levels increase with age in aortas, aortic vascular smooth muscle cells (VSMCs) and mitochondria, and are correlated with age-associated aortic stiffness in hypercholesterolemic mice. The present study investigated whether young mice (4 months-old) with increased mitochondrial NOX4 levels recapitulate vascular aging and age-associated aortic stiffness. We generated transgenic mice with low (Nox4TG605; 2.1-fold higher) and high (Nox4TG618; 4.9-fold higher) mitochondrial NOX4 expression. Young Nox4TG618 mice showed significant increase in aortic stiffness and decrease in phenylephrine-induced aortic contraction, but not Nox4TG605 mice. Increased mitochondrial oxidative stress increased intrinsic VSMC stiffness, induced aortic extracellular matrix remodeling and fibrosis, a leftward shift in stress-strain curves, decreased volume compliance and focal adhesion turnover in Nox4TG618 mice. Nox4TG618 VSMCs phenocopied other features of vascular aging such as increased DNA damage, increased premature and replicative senescence and apoptosis, increased proinflammatory protein expression and decreased respiration. Aortic stiffening in young Nox4TG618 mice was significantly blunted with mitochondrial-targeted catalase overexpression. This demonstration of the role of mitochondrial oxidative stress in aortic stiffness will galvanize search for new mitochondrial-targeted therapeutics for treatment of age-associated vascular dysfunction.
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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.