Asymmetric dimethylarginine in homocystinuria due to cystathionine β‐synthase deficiency: Relevance of renal function

Wilcken, D. E. L.; Wang, Jun; Sim, Ah Siew; Green, Kathryn; Wilcken, Bridget

doi:10.1007/s10545-006-0208-0

Cited by 23 publications

(13 citation statements)

References 43 publications

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“…The ADMA levels in our study population are in accordance with those of the others [20,[23][24][25]. In the dialysis patients, dimethylarginines were further increased: the SDMA concentration was about 3.5-fold higher in the early stage patients, whereas more than sevenfold higher both in PD and HD patients when compared to healthy controls.…”

Section: Discussionsupporting

confidence: 91%

Dimethylarginines and inflammation markers in patients with chronic kidney disease undergoing dialysis

et al. 2009

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The aim of this study was to investigate the pro-oxidant and proinflammatory biomarkers and their relationship with dimethylarginines (DMAs) in patients at various stages of chronic kidney disease (CKD). We studied 114 CKD patients, 36 were hemodialyzed, 41 peritoneal dialyzed and 37 nondialyzed (early stage) CKD patients. The control group consisted of 31 healthy subjects. Plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine, nitric oxide (NO) and proinflammatory cytokines (TNF-alpha and IL-6) were determined, and their relationships with the degree of disease were evaluated. Both DMAs were at high levels in all CKD patients, whereas arginine concentrations were low in patients undergoing dialysis. Elevated TNF-alpha and IL-6 in CKD patients were indicative of ongoing chronic inflammatory state. A significant positive correlation between SDMA and creatinine suggests that plasma SDMA level may be an index for renal function.

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Section: Discussionsupporting

confidence: 91%

Dimethylarginines and inflammation markers in patients with chronic kidney disease undergoing dialysis

et al. 2009

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“…In addition, the association between plasma ADMA and Hcy levels is observed in many animal and clinical studies. High Hcy concentrations might elevate ADMA by inhibiting dimethylarginine dimethylaminohydrolase (DDAH), the ADMA metabolizing enzyme, activity (Dayal & Lentz, 2005;Stühlinger et al, 2001;Wilcken et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The endothelium is the primary target of destruction arising from chemical and mechanical factors. Endothelial dysfunction, either as a cause or a consequence, is now known to be associated with a spectrum of cardiovascular diseases (Bestermann, 2011;Dayal & Lentz, 2005;Wilcken et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Beneficial effects of melatonin on serum nitric oxide, homocysteine, and ADMA levels in fructose-fed rats

Kantar

Türközkan

Bircan

et al. 2015

Pharmaceutical Biology

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“…This could underlie an impaired endothelium-dependent NO-mediated vasodilatation induced by homocysteine in the pig aorta (167). However, more recent data has shown that ADMA accumulates in patients with hyperhomocysteinemia only with the development of renal dysfunction (215).…”

Section: Expression and Function Of Ddah In Diseasementioning

confidence: 99%

Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems

Palm

Onozato²,

Luo³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

287

301

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Palm F, Onozato ML, Luo Z, Wilcox CS. Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems. Am J Physiol Heart Circ Physiol 293: H3227-H3245, 2007. First published October 12, 2007; doi:10.1152 doi:10. /ajpheart.00998.2007 )-dimethylarginine (ADMA) inhibits nitric oxide (NO) synthases (NOS). ADMA is a risk factor for endothelial dysfunction, cardiovascular mortality, and progression of chronic kidney disease. Two isoforms of dimethylarginine dimethylaminohydrolase (DDAH) metabolize ADMA. DDAH-1 is the predominant isoform in the proximal tubules of the kidney and in the liver. These organs extract ADMA from the circulation. DDAH-2 is the predominant isoform in the vasculature, where it is found in endothelial cells adjacent to the cell membrane and in intracellular vesicles and in vascular smooth muscle cells among the myofibrils and the nuclear envelope. In vivo gene silencing of DDAH-1 in the rat and DDAH ϩ/Ϫ mice both have increased circulating ADMA, whereas gene silencing of DDAH-2 reduces vascular NO generation and endothelium-derived relaxation factor responses. DDAH-2 also is expressed in the kidney in the macula densa and distal nephron. Angiotensin type 1 receptor activation in kidneys reduces the expression of DDAH-1 but increases the expression of DDAH-2. This rapidly evolving evidence of isoform-specific distribution and regulation of DDAH expression in the kidney and blood vessels provides potential mechanisms for nephron site-specific regulation of NO production. In this review, the recent advances in the regulation and function of DDAH enzymes, their roles in the regulation of NO generation, and their possible contribution to endothelial dysfunction in patients with cardiovascular and kidney diseases are discussed. nitric oxide synthase; hypertension; diabetes mellitus; chronic kidney disease; asymmetric dimethylarginineis an endogenous methylated amino acid that inhibits the constitutive endothelial (e) or type III and neuronal (n) or type I isoforms of nitric oxide (NO) synthase (NOS) (49,91,103,199). It is a less potent inhibitor of the inducible (i) or type II NOS isoform (41,191,213). Proteins are subject to methylation of arginine residues by protein arginine methyltransferase (PRMT). S-adenosylmethionine, which is synthesized from methionine and ATP, serves as the methyl donor and, in the process, is converted to S-adenosylhomocysteine, which itself can be hydrolyzed to homocysteine. Remethylation of homocysteine in the "remethylation pathway" regenerates methionine (14,179). ADMA is released by protein hydrolysis and exported from the cell and taken up by other cells via system y ϩ carriers of the cationic amino acid (CAT) family (14,196,212). ADMA is eliminated both by renal excretion and metabolic degradation. Its metabolism is facilitated by dimethylarginine dimethylaminohydrolases (DDAHs), which are expressed as type 1 and 2 isoforms. Recent studies have shown differential sites of expression of DDAH-1 and -2 in blo...

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Asymmetric dimethylarginine in homocystinuria due to cystathionine β‐synthase deficiency: Relevance of renal function

Abstract: ADMA levels were significantly increased only in the CBS-deficient patients with elevated cystatin C levels, and not in those with normal renal function. The reported relationship between hyperhomocysteinaemia and ADMA may not be direct, but could be secondary to reduced renal function.

Cited by 23 publications

References 43 publications

Dimethylarginines and inflammation markers in patients with chronic kidney disease undergoing dialysis

Dimethylarginines and inflammation markers in patients with chronic kidney disease undergoing dialysis

Beneficial effects of melatonin on serum nitric oxide, homocysteine, and ADMA levels in fructose-fed rats

Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems

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