ArticleJournal of translational medicine2013
Sildenafil restores endothelial function in the apolipoprotein E knockout mouse.
Article in Journal of translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Analysis of Phosphodiesterase-5 (PDE5) Inhibitors in Modulating Inflammatory Markers in Humans: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
- Heterogeneous Treatment Effects in HFpEF: Distinguishing Drug-Specific Response from Prognostic Phenotypes Across Randomized Trials.medRxiv : the preprint server for health sciences · 2026Article
- Article
- PACA nanoparticles target and deliver sildenafil to rejuvenate aged mouse liver sinusoidal endothelial cells.Nanotheranostics · 2025Article
- Administration of the KFrontiers in pharmacology · 2025Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Article
- Endothelial damage and dysfunction in acute graft-versus-host disease.Haematologica · 2021Article
- Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice.Frontiers in physiology · 2021Article
- The Phosphodiesterase Type 5 Inhibitor Sildenafil Improves DNA Stability and Redox Homeostasis in Systemic Sclerosis Fibroblasts Exposed to Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2020Article
- Sildenafil for the Treatment of Alzheimer's Disease: A Systematic Review.Journal of Alzheimer's disease reports · 2020Review
- Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress.The journal of sexual medicine · 2019Article
- Worsening of Oxidative Stress, DNA Damage, and Atherosclerotic Lesions in Aged LDLrOxidative medicine and cellular longevity · 2019Article
- Naringin Reverses High-Cholesterol Diet-Induced Vascular Dysfunction and Oxidative Stress in Rats via Regulating LOX-1 and NADPH Oxidase Subunit Expression.BioMed research international · 2019Article
- Increased ROS production and DNA damage in monocytes are biomarkers of aging and atherosclerosis.Biological research · 2018Article
- Crossroads between peripheral atherosclerosis, western-type diet and skeletal muscle pathophysiology: emphasis on apolipoprotein E deficiency and peripheral arterial disease.Journal of biomedical science · 2017Review
- The Therapeutic Potential of Anti-Inflammatory Exerkines in the Treatment of Atherosclerosis.International journal of molecular sciences · 2017Review
- The role of sildenafil in the development of transplant arteriosclerosis in rat aortic grafts.American journal of translational research · 2017Article
- Coadjuvants in the Diabetic Complications: Nutraceuticals and Drugs with Pleiotropic Effects.International journal of molecular sciences · 2016Review
- The effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline-induced right ventricular failure.Korean journal of pediatrics · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAtherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS) and nitric oxide (NO). Sildenafil, a selective phosphodiesterase-5 (PDE5) inhibitor used for erectile dysfunction, exerts its cardiovascular effects by enhancing the effects of NO. The aim of this study was to investigate the influence of sildenafil on endothelial function and atherosclerosis progression in apolipoprotein E knockout (apoE-/-) mice.
methodsApoE-/- mice treated with sildenafil (Viagra®, 40 mg/kg/day, for 3 weeks, by oral gavage) were compared to the untreated apoE-/- and the wild-type (WT) mice.Aortic rings were used to evaluate the relaxation responses to acetylcholine (ACh) in all of the groups. In a separate set of experiments, the roles of NO and ROS in the relaxation response to ACh were evaluated by incubating the aortic rings with L-NAME (NO synthase inhibitor) or apocynin (NADPH oxidase inhibitor). In addition, the atherosclerotic lesions were quantified and superoxide production was assessed.
resultsSildenafil restored the vasodilator response to acetylcholine (ACh) in the aortic rings of the apoE-/- mice. Treatment with L-NAME abolished the vasodilator responses to ACh in all three groups of mice and revealed an augmented participation of NO in the endothelium-dependent vasodilation in the sildenafil-treated animals. The normalized endothelial function in sildenafil-treated apoE-/- mice was unaffected by apocynin highlighting the low levels of ROS production in these animals. Moreover, morphological analysis showed that sildenafil treatment caused approximately a 40% decrease in plaque deposition in the aorta.
conclusionThis is the first study demonstrating the beneficial effects of chronic treatment with sildenafil on endothelial dysfunction and atherosclerosis in a model of spontaneous hypercholesterolemia. These data indicate that the main mechanism of the beneficial effect of sildenafil on the endothelial function appears to involve an enhancement of the NO pathway along with a reduction in oxidative stress.
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