scholarly journals The Second Life of Methylarginines as Cardiovascular Targets

2019 ◽  
Vol 20 (18) ◽  
pp. 4592 ◽  
Author(s):  
Natalia Jarzebska ◽  
Arduino A. Mangoni ◽  
Jens Martens-Lobenhoffer ◽  
Stefanie M. Bode-Böger ◽  
Roman N. Rodionov
Keyword(s):  
Second Life ◽  
Asymmetric Dimethylarginine ◽  
Research Direction ◽  
Research Field ◽  
Clinical Settings ◽  
Therapeutic Approaches ◽  
Symmetric Dimethylarginine ◽  
Relative Contribution ◽  
Endogenous Inhibitors ◽  
Glyoxylate Aminotransferase

Endogenous methylarginines were proposed as cardiovascular risk factors more than two decades ago, however, so far, this knowledge has not led to the development of novel therapeutic approaches. The initial studies were primarily focused on the endogenous inhibitors of nitric oxide synthases asymmetric dimethylarginine (ADMA) and monomethylarginine (MMA) and the main enzyme regulating their clearance dimethylarginine dimethylaminohydrolase 1 (DDAH1). To date, all the screens for DDAH1 activators performed with the purified recombinant DDAH1 enzyme have not yielded any promising hits, which is probably the main reason why interest towards this research field has started to fade. The relative contribution of the second DDAH isoenzyme DDAH2 towards ADMA and MMA clearance is still a matter of controversy. ADMA, MMA and symmetric dimethylarginine (SDMA) are also metabolized by alanine: glyoxylate aminotransferase 2 (AGXT2), however, in addition to methylarginines, this enzyme also has several cardiovascular protective substrates, so the net effect of possible therapeutic targeting of AGXT2 is currently unclear. Recent studies on regulation and functions of the enzymes metabolizing methylarginines have given a second life to this research direction. Our review discusses the latest discoveries and controversies in the field and proposes novel directions for targeting methylarginines in clinical settings.

scholarly journals Vascular function and arginine and dimethylarginines in gentamicin-induced renal failure: a possible effect of heme oxygenase 1 inducer hemin

2017 ◽  
Vol 95 (12) ◽  
pp. 1406-1413 ◽  
Author(s):  
Esra Aycan-Ustyol ◽  
Merve Kabasakal ◽  
Seldag Bekpinar ◽  
F. Ilkay Alp-Yıldırım ◽  
Ozge Tepe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Vascular Function ◽  
Asymmetric Dimethylarginine ◽  
Vascular Dysfunction ◽  
Cardiovascular Complication ◽  
Heme Oxygenase 1 ◽  
Antioxidant Enzyme Activities ◽  
Symmetric Dimethylarginine ◽  
Inflammatory Changes

Increased oxidative stress and disturbance in nitric oxide bioavailability lead to endothelial dysfunction and cardiovascular complication in renal disease. Gentamicin (GM), a commonly used antibiotic, exhibits a toxic effect on renal proximal tubules. Prevention of its nephrotoxicity is important. Therefore, we investigated whether heme oxygenase 1 HO-1) induction influenced kidney and vascular function in GM-administered rats. GM (100 mg·kg–1·day–1; i.p.) was given to rats alone or together with hemin (20 mg·kg–1 on alternate days; i.p.) for 14 days. Plasma and kidney l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) as well as kidney 4-hydroxynonenal (HNE) levels and myeloperoxidase (MPO) activity were measured. Histopathological examinations of kidney and relaxation and contraction responses of aorta were also examined. GM increased serum SDMA, urea nitrogen (BUN), and creatinine levels and caused histopathological alterations in the kidney. GM elevated HO-1 protein and mRNA expressions, 4-HNE level, and MPO activity and decreased antioxidant enzyme activities and l-arginine levels in the kidney. Decreased relaxation and contraction were detected in the aorta. Hemin restored renal oxidative stress and inflammatory changes together with vascular dysfunction, but did not affect SDMA, BUN, or creatinine levels. We conclude that HO-1 induction may be effective in improving renal oxidative stress, inflammation, and vascular dysfunction mediated by GM.

scholarly journals Increased Serum Levels of Asymmetric Dimethylarginine and Symmetric Dimethylarginine and Decreased Levels of Arginine in Sudanese Patients with Essential Hypertension

2020 ◽  
Vol 45 (5) ◽  
pp. 727-736
Author(s):  
Sahar Gamil ◽  
Jeanette Erdmann ◽  
Edzard Schwedhelm ◽  
Khalid Hussein Bakheit ◽  
Ihab B.B. Abdalrahman ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Essential Hypertension ◽  
Amino Acid ◽  
Asymmetric Dimethylarginine ◽  
Multivariate Logistic Regression Analysis ◽  
Serum Levels ◽  
Control Group ◽  
Multivariate Logistic Regression ◽  
Symmetric Dimethylarginine

Introduction: Essential hypertension (EH) is a disease caused by various environmental and genetic factors. Nitric oxide (NO) is important for the functional integrity of the endothelium. It is produced in endothelial cells by endothelial NO synthase (eNOS) that mediates the conversion of the amino acid arginine into NO and citrulline. Asymmetric dimethylarginine (ADMA) acts as an inhibitor of eNOS. In contrast, symmetric dimethylarginine (SDMA) has no direct effect on eNOS but plays an important role competing with arginine for transport across the amino acid transporter. ADMA and SDMA have been found to play a central role in the development of cardiovascular diseases. Serum ADMA levels may serve as a future diagnostic marker and a target of therapy in hypertensive patients in the Sudanese population. This study aimed to investigate the relation between serum arginine, ADMA, and SDMA levels with EH in the Sudanese population. Methods: Patients (n = 260) with established hypertension and controls (n = 144) with normal blood pressure were included in this case-control study. Serum blood samples were analyzed for arginine, ADMA, and SDMA, using high-performance liquid chromatography-tandem mass spectrometry. Other laboratory data were measured using routine methods. Mann-Whitney’s U test and χ2 tests were used for continuous and categorical data, respectively. A multivariate logistic regression analysis was conducted to investigate the independent effect of multiple variables on the development of hypertension. Results: Serum arginine levels were significantly lower in the patient group than in the control group (p < 0.001). ADMA and SDMA levels were significantly higher in the patient group than the control group (p < 0.001, p = 0.001, respectively). Multivariate logistic regression analysis showed that only older age, being a male, and arginine levels are independent factors controlling the development of hypertension (p < 0.001, p < 0.001, and p = 0.046, respectively). ADMA and SDMA levels were not independent factors for the development of hypertension. Conclusions: This study demonstrated increased serum levels of ADMA and SDMA and decreased arginine levels in Sudanese patients with EH. Lowering serum ADMA levels or increasing the arginine levels might be a novel therapeutic target in these individuals.

scholarly journals Asymmetric Dimethylarginine (ADMA) and Symmetric Dimethylarginine (SDMA) Concentrations in Patients with Obesity and the Risk of Obstructive Sleep Apnea (OSA)

2019 ◽  
Vol 8 (6) ◽  
pp. 897 ◽  
Author(s):  
Yana Arlouskaya ◽  
Ada Sawicka ◽  
Marek Głowala ◽  
Joanna Giebułtowicz ◽  
Natalia Korytowska ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Asymmetric Dimethylarginine ◽  
Apnea Hypopnea Index ◽  
Enos Gene ◽  
No Production ◽  
Serum Concentrations ◽  
Symmetric Dimethylarginine ◽  
Obstructive Sleep

Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous inhibitors of nitric oxide (NO) synthesis, and play a critical role in the process of endothelial dysfunction, and are considered markers of oxidative stress. The aim of the present study was to explore relationships between ADMA and/or SDMA and the occurrence of OSA in obese patients as well as the effect of the endothelial nitric oxide synthase (eNOS) gene polymorphism, which may modify the influence of ADMA or SDMA on NO production. A total of 518 unrelated obese subjects were included in this study. Body weight, height and blood pressure were measured and data on self-reported smoking status were collected. Obstructive sleep apnea (OSA) was assessed by the apnea hypopnea index (AHI). Blood samples were collected to measure serum concentrations of glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, creatinine, HbA1c (%), folic acid, vitamin B12, C-reactive protein (CRP), aspartate aminotransferase (ASP), alanine aminotransferase (ALT) and IL-6 by routine methods. The NOS3 gene G894T and 4a/4b polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. ADMA, SDMA and arginine concentrations were assessed simultaneously using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method. Adjusted multivariate logistic regression analysis showed a significant association between the occurrence of OSA and high serum ADMA levels, BMI above 40, age > 43 years, hypertension and male sex. Heterozygotes for the G894T eNOS polymorphism have the lowest serum concentrations of ADMA and SDMA, while no effect of the 4a/4b variants was observed. The results indicate that OSA in obese individuals can coexist with high ADMA levels, which appear as a potential OSA predictor.

scholarly journals A Yeast-Based Model for Hereditary Motor and Sensory Neuropathies: A Simple System for Complex, Heterogeneous Diseases

2020 ◽  
Vol 21 (12) ◽  
pp. 4277 ◽  
Author(s):  
Weronika Rzepnikowska ◽  
Joanna Kaminska ◽  
Dagmara Kabzińska ◽  
Katarzyna Binięda ◽  
Andrzej Kochański
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Diagnosis ◽  
Clinical Manifestations ◽  
Model System ◽  
Research Field ◽  
Therapeutic Approaches ◽  
Rare Disorders ◽  
Advantages And Disadvantages ◽  
Pathogenic Variants ◽  
Disease Subtypes

Charcot–Marie–Tooth (CMT) disease encompasses a group of rare disorders that are characterized by similar clinical manifestations and a high genetic heterogeneity. Such excessive diversity presents many problems. Firstly, it makes a proper genetic diagnosis much more difficult and, even when using the most advanced tools, does not guarantee that the cause of the disease will be revealed. Secondly, the molecular mechanisms underlying the observed symptoms are extremely diverse and are probably different for most of the disease subtypes. Finally, there is no possibility of finding one efficient cure for all, or even the majority of CMT diseases. Every subtype of CMT needs an individual approach backed up by its own research field. Thus, it is little surprise that our knowledge of CMT disease as a whole is selective and therapeutic approaches are limited. There is an urgent need to develop new CMT models to fill the gaps. In this review, we discuss the advantages and disadvantages of yeast as a model system in which to study CMT diseases. We show how this single-cell organism may be used to discriminate between pathogenic variants, to uncover the mechanism of pathogenesis, and to discover new therapies for CMT disease.

High clinical accuracy of asymmetric dimethylarginine and symmetric dimethylarginine in patients with ischemic heart disease

Amino Acids ◽  
2012 ◽  
Vol 43 (6) ◽  
pp. 2293-2300 ◽  
Author(s):  
B. V. Djordjević ◽  
R. Pavlović ◽  
V. Ćosić ◽  
M. Deljanin-Ilić ◽  
T. Ristić ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Asymmetric Dimethylarginine ◽  
Ischemic Heart ◽  
Symmetric Dimethylarginine ◽  
Clinical Accuracy

Asymmetric dimethylarginine is not elevated in exfoliation syndrome but symmetric dimethylarginine is related to exfoliative glaucoma

2006 ◽  
Vol 245 (2) ◽  
pp. 204-209 ◽  
Author(s):  
Hillevi Blomster ◽  
Tuomo Puustjärvi ◽  
Matti Kontkanen ◽  
Pirjo Valtonen ◽  
Markku Teräsvirta ◽  
...  
Keyword(s):  
Asymmetric Dimethylarginine ◽  
Exfoliation Syndrome ◽  
Symmetric Dimethylarginine ◽  
Exfoliative Glaucoma

Application of Inorganic Ceramic Membrane in Wastewater Treatment I: Process Research and Parameter Optimization

2013 ◽  
Vol 454 ◽  
pp. 158-162 ◽  
Author(s):  
Guo Yi Li ◽  
Xiao Hui Wang ◽  
Yan Jie Wei
Keyword(s):  
Ceramic Membrane ◽  
High Strength ◽  
Research Direction ◽  
Research Field ◽  
Alkali Resistance ◽  
Future Research ◽  
Chemical Additives ◽  
Mechanical Metallurgy ◽  
Acid And Alkali Resistance ◽  
Automation Control

Inorganic ceramic membrane has been one of the hottest research field both in environmental protection and materials, as it has so much advantages, such as, high-temperature-resistance ,acid and alkali-resistance , adequate distribution of aperture , steady chemical property , high strength , large flux, long lifetime, anti-pollution, simple structure, small footprint, few corollary equipment, easy installation, no chemical additives, high separating efficiency, high degree of automation control and so on. Some application on environmental progress in the field of inorganic ceramic membrane technology applied in treatment of food industry wastewater, mechanical metallurgy wastewater and petrochemical wastewater was summarized in this paper, and the existent problems and the future research direction was discussed.

Sign in / Sign up

Export Citation Format

Share Document