Genome-wide association study of L-arginine and dimethylarginines reveals novel metabolic pathway for symmetric dimethylarginine.

Background: Dimethylarginines (DMA) interfere with nitric oxide formation by inhibiting nitric oxide synthase (asymmetrical DMA [ADMA]) and l-arginine uptake into the cell (ADMA and symmetrical DMA [SDMA]). In prospective clinical studies, ADMA has been characterized as a cardiovascular risk marker, whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterize the environmental and genetic contributions to interindividual variability of these biomarkers.

Genetic and environmental determinants of dimethylarginines and association with cardiovascular disease in patients with type 2 diabetes.

Objective: To investigate determinants of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), including single nucleotide polymorphisms (SNPs), in the DDAH1, DDAH2, and AGXT2 genes and their associations with prevalent and incident cardiovascular disease (CVD) in older adults with type 2 diabetes mellitus.

Research Design And Methods: Prevalent CVD was assessed in men and women aged 60-75 years with type 2 diabetes as part of the Edinburgh Type 2 Diabetes Study (ET2DS), and the participants were prospectively followed up for 4 years for incident CVD. Dimethylarginines were measured in 783 of these subjects, and genotyping for tag SNPs in the DDAH1, DDAH2, and AGXT2 genes was performed in 935 subjects.

Symmetrical dimethylarginine predicts mortality in the general population: observations from the Dallas heart study.

Objective: Increased asymmetrical dimethylarginine (ADMA), a NO synthase inhibitor, and its congener symmetrical dimethylarginine (SDMA), predict cardiovascular and all-cause mortality in at-risk populations. Their prognostic value in the general population remains uncertain. We investigated the correlations of SDMA and ADMA with atherosclerosis and cardiovascular/all-cause mortality in the Dallas Heart Study, a multiethnic probability-based cohort aged 30 to 65 years.

FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats.

Aims: Genetic and pharmacological studies have shown that impairment of the nitric oxide (NO) synthase (NOS) pathway is associated with hypertension and insulin-resistance (IR). In addition, inhibition of NOS by the endogenous inhibitor, asymmetric dimethylarginine (ADMA), may also result in hypertension and IR. On the other hand, overexpression of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes ADMA, in mice is associated with lower ADMA, increased NO and enhanced insulin sensitivity.

The L-Arginine-asymmetric dimethylarginine ratio is an independent predictor of mortality in dilated cardiomyopathy.

Background: Asymmetric dimethylarginine (ADMA) is associated with increased mortality in patients with chronic heart failure but it remains unclear if the etiology of heart failure influences the prognostic value of dimethylarginines.

Methods And Results: L-Arginine, ADMA, and symmetric dimethylarginine (SDMA) were measured by liquid chromatography-tandem mass spectrometry in 341 patients with chronic heart failure due to dilated cardiomyopathy (DCM; n = 226) or ischemic cardiomyopathy (ICM; n = 115). Median (interquartile range [IQR]) ADMA and SDMA plasma levels were higher, L-arginine and the L-arginine-ADMA ratio were lower in patients with severe forms of heart failure (New York Heart Association (NYHA) functional class III or IV) compared with milder forms (NYHA functional class I or II) (ADMA 0.

Severely decreased activity of placental dimethylarginine dimethylaminohydrolase in pre-eclampsia.

Objectives: Asymmetric dimethylarginine (ADMA) is a key regulator of nitric oxide production. Elevations of ADMA have previously been associated with endothelial dysfunction in pre-eclamptic women. ADMA is degraded mainly by dimethylarginine dimethylaminohydrolase (DDAH), which is also expressed in placental tissue.

Reference intervals for plasma L-arginine and the L-arginine:asymmetric dimethylarginine ratio in the Framingham Offspring Cohort.

L-arginine, as a precursor of NO synthesis, has attracted much scientific attention in recent years. Experimental mouse models suggest that L-arginine supplementation can retard, halt, or even reverse atherogenesis. In human studies, supplementation with L-arginine improved endothelium-dependent vasodilation.

Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality: an intriguing interaction with diabetes mellitus.

Asymmetric dimethylarginine (ADMA) has evolved as an important regulator of nitric oxide (NO) synthesis in recent years. Elevated levels of ADMA have been reported in many conditions associated with a high cardiovascular risk. Moreover, ADMA is a biomarker for major cardiovascular events and mortality in cohorts with high, intermediate and low overall cardiovascular risk.

Dimethylarginines: their vascular and metabolic roles in Africans and Caucasians.

Objective: Alarming increases in hypertension and type 2 diabetes among Africans accentuate the need to identify factors that could serve as targets for prevention or treatment. In Caucasian populations, asymmetric dimethylarginine (ADMA), the predominant endogenous nitric oxide synthase inhibitor, is associated with cardiovascular disease and insulin resistance (IR). ADMA's counterpart, symmetric dimethylarginine (SDMA), originally thought to be inert, was recently also linked with cardiovascular risk.