ArticleAmerican journal of physiology. Heart and circulatory physiology2016
Early life stress in male mice induces superoxide production and endothelial dysfunction in adulthood.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Impact of Early Postnatal Maternal Separation Stress on Pancreatic Function in Rodents: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
- Early life stress blunts time-of-day-specific autonomic function in adult male mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Article
- A history of maternal separation drives systemic aging-associated signatures in middle-aged male rats.Frontiers in cellular neuroscience · 2026Article
- Neonatal stress disrupts the glymphatic system development and increases the susceptibility to Parkinson's disease in later life.CNS neuroscience & therapeutics · 2024Article
- N-Acetylcysteine Alleviates Depressive-Like Behaviors in Adolescent EAAC1International journal of biological sciences · 2024Article
- Association of early life adversity with cardiovascular disease and its potential mechanisms: a narrative review.Frontiers in public health · 2024Review
- Early Life Stress in Mice Leads to Impaired Colonic Corticosterone Production and Prolonged Inflammation Following Induction of Colitis.Inflammatory bowel diseases · 2023Article
- Porcine blood cell and brain tissue energy metabolism: Effects of "early life stress".Frontiers in molecular biosciences · 2023Article
- How do Adverse Childhood Experiences get Under the Skin to Promote Cardiovascular Disease? A Focus on Vascular Health.Function (Oxford, England) · 2022Article
- The Link Between Childhood Adversity and Cardiovascular Disease Risk: Role of Cerebral and Systemic Vasculature.Function (Oxford, England) · 2022Article
- Childhood psychosocial stress is linked with impaired vascular endothelial function, lower SIRT1, and oxidative stress in young adulthood.American journal of physiology. Heart and circulatory physiology · 2021Article
- Adverse childhood events and cardiovascular diseases: the potential role of Sirt1.American journal of physiology. Heart and circulatory physiology · 2021Article
- Biological Connection of Psychological Stress and Polytrauma under Intensive Care: The Role of Oxytocin and Hydrogen Sulfide.International journal of molecular sciences · 2021Review
- Long-term cerebrovascular dysfunction in the offspring from maternal electronic cigarette use during pregnancy.American journal of physiology. Heart and circulatory physiology · 2021Article
- Liver circadian clock disruption alters perivascular adipose tissue gene expression and aortic function in mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Oxidative Dysregulation in Early Life Stress and Posttraumatic Stress Disorder: A Comprehensive Review.Brain sciences · 2021Review
- Early life stress in mice alters gut microbiota independent of maternal microbiota inheritance.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Early life stress induces dysregulation of the heme pathway in adult mice.Physiological reports · 2021Article
- Nitric oxide and oxidative stress pathways do not contribute to sex differences in renal injury and function in Dahl SS/Jr rats.Physiological reports · 2020Article
- Maternal Separation Induces Long-Term Alterations in the Cardiac Oxytocin Receptor and CystathionineOxidative medicine and cellular longevity · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Early life stress (ELS) is a risk for cardiovascular disease in adulthood although very little mechanistic insight is available. Because oxidative stress and endothelial dysfunction are major contributors to cardiovascular risk, we hypothesized that ELS induces endothelial dysfunction in adult male mice via increased superoxide production. Studies employed a mouse model of ELS, maternal separation with early weaning (MSEW), in which litters were separated from the dam for 4 h/day [postnatal days (PD) 2-5] and 8 h/day (PD6-16), and weaned at PD17. Control litters remained undisturbed until weaning at PD21. When compared with control mice, thoracic aortic rings from adult male MSEW mice displayed significant endothelial dysfunction that was reversed by the superoxide scavenger, polyethylene glycol-superoxide dismutase (PEG-SOD). PEG-SOD-inhibitable superoxide production by aortae from MSEW mice was significantly greater than observed in control aortae, although unaffected by nitric oxide synthase inhibition, suggesting that uncoupled nitric oxide synthase was not responsible for the accelerated superoxide production. Aortic SOD expression, plasma SOD activity, and total antioxidant activity were similar in MSEW and control mice, indicating unaltered antioxidant capacity in MSEW mice. Increased expression of the NADPH oxidase subunits, NOX2 and NOX4, was evident in the aortae of MSEW mice. Moreover, endothelial dysfunction and superoxide production in MSEW mice was reversed with the NADPH oxidase inhibitor, apocynin, indicating increased NADPH oxidase-dependent superoxide production and endothelial dysfunction. The finding that MSEW induces superoxide production and endothelial dysfunction in adult mice may provide a mechanistic link between ELS and adult cardiovascular disease risk.
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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.