ArticlePLoS pathogens2015
Plasmodium Infection Is Associated with Impaired Hepatic Dimethylarginine Dimethylaminohydrolase Activity and Disruption of Nitric Oxide Synthase Inhibitor/Substrate Homeostasis.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Sickle Trait and Alpha Thalassemia Increase NOS-Dependent Vasodilation of Human Arteries Through Disruption of Endothelial Hemoglobin-eNOS Interactions.Circulation · 2025Article
- Review
- Oxidative Stress in Malaria: Potential Benefits of Antioxidant Therapy.International journal of molecular sciences · 2022Review
- Decreased parasite burden and altered host response in children with sickle cell anemia and severe anemia with malaria.Blood advances · 2021Article
- DDAH-1, via regulation of ADMA levels, protects against ischemia-induced blood-brain barrier leakage.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- L-arginine supplementation and thromboxane synthase inhibition increases cerebral blood flow in experimental cerebral malaria.Scientific reports · 2019Article
- Perspective: L-arginine and L-citrulline Supplementation in Pregnancy: A Potential Strategy to Improve Birth Outcomes in Low-Resource Settings.Advances in nutrition (Bethesda, Md.) · 2019Review
- Kinetic and Cross-Sectional Studies on the Genesis of Hypoargininemia in Severe PediatricInfection and immunity · 2019Observational
- Malaria in pregnancy alters l-arginine bioavailability and placental vascular development.Science translational medicine · 2018Article
- Decreased Rate of Plasma Arginine Appearance in Murine Malaria May Explain Hypoargininemia in Children With Cerebral Malaria.The Journal of infectious diseases · 2016Article
- Nitric Oxide-Dependent Endothelial Dysfunction and Reduced Arginine Bioavailability in Plasmodium vivax Malaria but No Greater Increase in Intravascular Hemolysis in Severe Disease.The Journal of infectious diseases · 2016Article
- Tetrahydrobiopterin Supplementation Improves Phenylalanine Metabolism in a Murine Model of Severe Malaria.ACS infectious diseases · 2016Article
- Article
- Pathophysiological Mechanisms in Gaseous Therapies for Severe Malaria.Infection and immunity · 2016Review
- Asymmetric Dimethylarginine in Adult Falciparum Malaria: Relationships With Disease Severity, Antimalarial Treatment, Hemolysis, and Inflammation.Open forum infectious diseases · 2016Article
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 3 countries.
Funding
Abstract
Inhibition of nitric oxide (NO) signaling may contribute to pathological activation of the vascular endothelium during severe malaria infection. Dimethylarginine dimethylaminohydrolase (DDAH) regulates endothelial NO synthesis by maintaining homeostasis between asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor, and arginine, the NOS substrate. We carried out a community-based case-control study of Gambian children to determine whether ADMA and arginine homeostasis is disrupted during severe or uncomplicated malaria infections. Circulating plasma levels of ADMA and arginine were determined at initial presentation and 28 days later. Plasma ADMA/arginine ratios were elevated in children with acute severe malaria compared to 28-day follow-up values and compared to children with uncomplicated malaria or healthy children (p<0.0001 for each comparison). To test the hypothesis that DDAH1 is inactivated during Plasmodium infection, we examined DDAH1 in a mouse model of severe malaria. Plasmodium berghei ANKA infection inactivated hepatic DDAH1 via a post-transcriptional mechanism as evidenced by stable mRNA transcript number, decreased DDAH1 protein concentration, decreased enzyme activity, elevated tissue ADMA, elevated ADMA/arginine ratio in plasma, and decreased whole blood nitrite concentration. Loss of hepatic DDAH1 activity and disruption of ADMA/arginine homeostasis may contribute to severe malaria pathogenesis by inhibiting NO synthesis.
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