ArticleJournal of molecular and cellular cardiology2015
Liposomal tetrahydrobiopterin preserves eNOS coupling in the post-ischemic heart conferring in vivo cardioprotection.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Atrial nitroso-redox balance and refractoriness following on-pump cardiac surgery: a randomized trial of atorvastatin.Cardiovascular research · 2022Trial
- Blocking MyD88 Signaling Pathway Protects Against Myocardial Ischemia Reperfusion by Inhibiting NOX/ROS Pathway and Enhancing eNOS Activity.International journal of molecular sciences · 2026Article
- The pleiotropic effects of statins: a comprehensive exploration of neurovascular unit modulation and blood-brain barrier protection.Molecular medicine (Cambridge, Mass.) · 2024Review
- Replicative Endothelial Cell Senescence May Lead to Endothelial Dysfunction by Increasing the BH2/BH4 Ratio Induced by Oxidative Stress, Reducing BH4 Availability, and Decreasing the Expression of eNOS.International journal of molecular sciences · 2024Article
- Protein arginine methyltransferase 4 modulates nitric oxide synthase uncoupling and cerebral blood flow in Alzheimer's disease.Journal of cellular physiology · 2024Article
- Tetrahydrobiopterin metabolism attenuates ROS generation and radiosensitivity through LDHA S-nitrosylation: novel insight into radiogenic lung injury.Experimental & molecular medicine · 2024Article
- Nanomedicine-Based Therapeutics for Myocardial Ischemic/Reperfusion Injury.Advanced healthcare materials · 2023Review
- Endothelial cell-specific roles for tetrahydrobiopterin in myocardial function, cardiac hypertrophy, and response to myocardial ischemia-reperfusion injury.American journal of physiology. Heart and circulatory physiology · 2023Article
- Targeting Reactive Oxygen Species in Atherosclerosis via Chinese Herbal Medicines.Oxidative medicine and cellular longevity · 2022Review
- The Critical Role of Tetrahydrobiopterin (BH4) Metabolism in Modulating Radiosensitivity: BH4/NOS Axis as an Angel or a Devil.Frontiers in oncology · 2021Review
- Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments.Oxidative medicine and cellular longevity · 2021Review
- Chronic cigarette smoke exposure triggers a vicious cycle of leukocyte and endothelial-mediated oxidant stress that results in vascular dysfunction.American journal of physiology. Heart and circulatory physiology · 2020Article
- Roles of eNOS in atherosclerosis treatment.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
- Nitric oxide signalling in cardiovascular health and disease.Nature reviews. Cardiology · 2018Review
- Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling.Scientific reports · 2017Article
- Impaired Endothelial Nitric Oxide Synthase Homodimer Formation Triggers Development of Transplant Vasculopathy - Insights from a Murine Aortic Transplantation Model.Scientific reports · 2016Article
- Reperfusion injury and reactive oxygen species: The evolution of a concept.Redox biology · 2015Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS), and reduced BH4 availability leads to endothelial NOS (eNOS) uncoupling and increased reactive oxygen species (ROS) generation. Questions remain regarding the functional state of eNOS and role of BH4 availability in the process of in vivo myocardial ischemia-reperfusion (I/R) injury. Rats were subjected to 60min of in vivo left coronary artery occlusion and varying periods of reperfusion with or without pre-ischemic liposomal BH4 supplementation (1mg/kg, iv). Myocardial infarction was correlated with cardiac BH4 content, eNOS protein level, NOS enzyme activity, and ROS generation. In the vehicle group, 60-min ischemia drastically reduced myocardial BH4 content in the area at risk (AAR) compared to non-ischemic (NI) area and the level remained lower during early reperfusion followed by recovery after 24-h reperfusion. Total eNOS, activated eNOS protein level (eNOS Ser1177 phosphorylation) and NOS activity were also significantly reduced during ischemia and/or early reperfusion, but recovered after 24-h reperfusion. With liposomal BH4 treatment, BH4 levels were identical in the AAR and NI area during ischemia and/or early reperfusion, and were significantly higher than with vehicle. BH4 pre-treatment preserved eNOS Ser1177 phosphorylation and NOS activity in the AAR, and significantly reduced myocardial ROS generation and infarction compared to vehicle. These findings provide direct evidence that in vivo I/R induces eNOS dysfunction secondary to BH4 depletion, and that pre-ischemic liposomal BH4 administration preserves eNOS function conferring cardioprotection with reduced oxidative stress.
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