ArticleAmerican journal of physiology. Heart and circulatory physiology2010
Regulation of the ADMA-DDAH system in endothelial cells: a novel mechanism for the sterol response element binding proteins, SREBP1c and -2.
Article in American journal of physiology. Heart and circulatory physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations.Scientific reports · 2015Pooled it
- Protein arginine methyltransferases in cardiovascular disease: mechanisms, therapeutic potential, and future directions.Frontiers in physiology · 2026Review
- Regulatory effects of resveratrol on nitric oxide signaling in cardiovascular diseases.Pharmacological reports : PR · 2025Review
- Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets.Cellular & molecular biology letters · 2023Article
- Blond and blood juice supplementation in high fat diet fed mice: effect on antioxidant status and DDAH/ADMA pathway.RSC advances · 2019Article
- Inhibition of Dimethylarginine Dimethylaminohydrolase (DDAH) Enzymes as an Emerging Therapeutic Strategy to Target Angiogenesis and Vasculogenic Mimicry in Cancer.Frontiers in oncology · 2019Review
- Inhibitors of the Hydrolytic Enzyme Dimethylarginine Dimethylaminohydrolase (DDAH): Discovery, Synthesis and Development.Molecules (Basel, Switzerland) · 2016Review
- Serum trans fatty acids, asymmetric dimethylarginine and risk of acute myocardial infarction and mortality in patients with suspected coronary heart disease: a prospective cohort study.Lipids in health and disease · 2016Article
- Integrative Mouse and Human Studies Implicate ANGPT1 and ZBTB7C as Susceptibility Genes to Ischemic Injury.Stroke · 2015Article
- Strategies to increase nitric oxide signalling in cardiovascular disease.Nature reviews. Drug discovery · 2015Review
- The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine.International journal of molecular sciences · 2015Article
- Statins in Asthma: Potential Beneficial Effects and Limitations.Pulmonary medicine · 2015Review
- Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease.EMBO molecular medicine · 2014Review
- The endothelial ADMA/NO pathway in hypoxia-related chronic respiratory diseases.BioMed research international · 2014Review
- Omega-3 Status and the Relationship between Plasma Asymmetric Dimethylarginine and Risk of Myocardial Infarction in Patients with Suspected Coronary Artery Disease.Cardiology research and practice · 2012Article
- Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and lessons from the recent clinical trials.Current pharmaceutical design · 2012Review
- Simvastatin inhibits goblet cell hyperplasia and lung arginase in a mouse model of allergic asthma: a novel treatment for airway remodeling?Translational research : the journal of laboratory and clinical medicine · 2010Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Asymmetric dimethylarginine (ADMA) has been implicated in the progression of cardiovascular disease as an endogenous inhibitor of nitric oxide synthase. The regulation of dimethylarginine dimethylaminohydrolase (DDAH), the enzyme responsible for metabolizing ADMA, is poorly understood. The transcription factor sterol response element binding protein (SREBP) is activated by statins via a reduction of membrane cholesterol content. Because the promoters of both DDAH1 and DDAH2 isoforms contain sterol response elements, we tested the hypothesis that simvastatin regulates DDAH1 and DDAH2 transcription via SREBP. In cultured endothelial cells, simvastatin increased DDAH1 mRNA expression compared with vehicle. In an ADMA loading experiment, simvastatin treatment resulted in a decrease in ADMA content, an indication of increased DDAH activity. The knockdown of SREBP1c protein led to an increase in DDAH1 mRNA expression and activity, whereas the knockdown of SREBP2 led to a decrease in DDAH1 mRNA expression. The role of SREBP2 in the activation of the DDAH1 was supported by chromatin immunoprecipitation studies demonstrating increased binding of SREBP2 to the DDAH1 promoter upon simvastatin stimulation. These data indicate that SREBP1c might act as a repressor and SREBP2 as an activator of DDAH transcription and activity. This study describes a novel mechanism of reciprocal regulation by the SREBP family members of the DDAH-ADMA system, which represents a potential link between cellular cholesterol content and endothelial dysfunction observed in cardiovascular disease.
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Registered trials
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