Effect of Shear Stress on Asymmetric Dimethylarginine Release From Vascular Endothelial Cells

Osanai, Tomohiro; Saitoh, Masayuki; Sasaki, Satoshi; Tomita, Hirofumi; Matsunaga, Toshiro; Okumura, Ken

doi:10.1161/01.hyp.0000097805.05108.16

Cited by 105 publications

(73 citation statements)

References 37 publications

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“…Endothelial shear and high LDL concentrations do, however, upregulate PRMT1, thereby increasing ADMA release. 71,72 Oxidative stress, as occurs in CKD, 19 is associated with enhanced ADMA synthesis via stimulation of PRMT1. 71 At present, however, regulation of ADMA levels in relation to cardiovascular control is thought to be mainly a function of ADMA clearance.…”

Section: Regulation Of Adma Levelsmentioning

confidence: 99%

Arginine, arginine analogs and nitric oxide production in chronic kidney disease

2006

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SummaryNitric oxide (NO) production is reduced in renal disease, partially due to decreased endothelial NO production. Evidence indicates that NO deficiency contributes to cardiovascular events and progression of kidney damage. Two possible causes of NO deficiency are substrate (L-arginine) limitation and increased levels of circulating endogenous inhibitors of NO synthase (particularly asymmetric dimethylarginine [ADMA]). Decreased L-arginine availability in chronic kidney disease (CKD) is due to perturbed renal biosynthesis of this amino acid. In addition, inhibition of transport of L-arginine into endothelial cells and shunting of L-arginine into other metabolic pathways (e.g. those involving arginase) might also decrease availability. Elevated plasma and tissue levels of ADMA in CKD are functions of both reduced renal excretion and reduced catabolism by dimethylarginine dimethylaminohydrolase (DDAH). The latter might be associated with loss-offunction polymorphisms of a DDAH gene, functional inhibition of the enzyme by oxidative stress in CKD and end-stage renal disease, or both. These findings provide the rationale for novel therapies, including supplementation of dietary L-arginine or its precursor L-citrulline, inhibition of non-NOproducing pathways of L-arginine utilization, or both. Because an increase in ADMA has emerged as a major independent risk factor in end-stage renal disease (and probably also in CKD), lowering ADMA concentration is a major therapeutic goal; interventions that enhance the activity of the ADMA-hydrolyzing enzyme DDAH are under investigation.

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Section: Regulation Of Adma Levelsmentioning

confidence: 99%

Arginine, arginine analogs and nitric oxide production in chronic kidney disease

2006

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“…Increased activity of PRMT1 has been demonstrated following moderate levels of shear stress, which can be attenuated by IκB kinase A or the PPARγ activator, troglitazone [28]. The action of shear stress upon PRMT1 is attributed to the action of NFγB response element, and following shear stress increased levels of methylarginines have been measured [28]. Similar levels of shear stress have been shown to activate eNOS through AKTphosphorylation [29,30].…”

Section: Adma Synthesismentioning

confidence: 99%

“…Both oxidised and normal low-density lipoprotein (LDL) increase the expression of PRMT1, PRMT2 and PRMT3 [27]. Increased activity of PRMT1 has been demonstrated following moderate levels of shear stress, which can be attenuated by IκB kinase A or the PPARγ activator, troglitazone [28]. The action of shear stress upon PRMT1 is attributed to the action of NFγB response element, and following shear stress increased levels of methylarginines have been measured [28].…”

Section: Adma Synthesismentioning

confidence: 99%

“…ADMA levels were observed to rise in the presence of either oxidised LDL or tumour necrosis factor-α, which was accompanied by a fall in DDAH activity [51]. DDAHI expression was increased in an in vivo model correlating with area of low blood flow in the heart [52], shear stress has been demonstrated to effect PRMT activity [28].…”

Section: Manipulation Of Ddah Expressionmentioning

confidence: 99%

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Cardiovascular Tests: Use & Limits of Biochemical Markers - Therapeutic Measurements of ADMA Involved in Cardiovascular Disorders

Smith¹,

Vallance²

2005

CPD

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“…Blood flow may exert an affect on DDAH expression, low blood flow in the heart correlated with increased DDAHI expression and shear stress has been reported to alter PRMT activity [158] as well as activating eNOS [159]. Finally, there have been reports that oestrogen replacement reduced plasma concentrations of ADMA [160], oestrogen has been demonstrated to increase DDAH activity and to reduce concentrations of ADMA [155].…”

Section: Regulation Of Adma Metabolismmentioning

confidence: 99%

C-Reactive Protein and Asymmetric Dimethylarginine: Markers or Mediators in Cardiovascular Disorders?

Smith¹

2007

CPD

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This is an electronic version of an article published in Current Pharmaceutical Design, 13 (16). pp. [1619][1620][1621][1622][1623][1624][1625][1626][1627][1628][1629] 2007. The definitive version is available online at:http://www.bentham.org/cpd/index.htmThe WestminsterResearch online digital archive at the University of Westminster aims to make the research output of the University available to a wider audience. Copyright and Moral Rights remain with the authors and/or copyright owners. Users are permitted to download and/or print one copy for non-commercial private study or research. Further distribution and any use of material from within this archive for profit-making enterprises or for commercial gain is strictly forbidden.Whilst further distribution of specific materials from within this archive is forbidden, you may freely distribute the URL of WestminsterResearch.(http://www.wmin.ac.uk/westminsterresearch).In case of abuse or copyright appearing without permission e-mail wattsn@wmin.ac.uk. Abstract: C-reactive protein (CRP) has received much attention as a cardiovascular risk factor and has been recommended to be used in screening to assist in predicting the occurrence of cardiovascular disorders. There are numerous association studies documenting changes in circulating CRP concentrations, there are, however, fewer studies providing evidence that CRP mediates the progression of cardiovascular pathologies. Elucidating the potential mechanisms for CRP has been confounded by recent reports that contaminants of CRP are partially responsible for observed effects.In this review the use of CRP as a tool to predict cardiovascular disorders will be discussed alongside a more recently described cardiovascular risk factor asymmetric dimethylarginine (ADMA). An endogenously occurring nitric oxide synthase inhibitor, ADMA, is formed by the action of protein arginine methyltransferases and subsequent proteolysis and it is metabolised in vivo by the dimethylarginine dimethylaminohydrolases (DDAH). The evidence available documenting the effects of CRP and ADMA, the regulatory mechanisms and the genetic influences, will be discussed in order to determine whether CRP and ADMA are mediators in the progression of cardiovascular disorders or merely useful biomarkers.

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Effect of Shear Stress on Asymmetric Dimethylarginine Release From Vascular Endothelial Cells

Cited by 105 publications

References 37 publications

Arginine, arginine analogs and nitric oxide production in chronic kidney disease

Arginine, arginine analogs and nitric oxide production in chronic kidney disease

Cardiovascular Tests: Use & Limits of Biochemical Markers - Therapeutic Measurements of ADMA Involved in Cardiovascular Disorders

C-Reactive Protein and Asymmetric Dimethylarginine: Markers or Mediators in Cardiovascular Disorders?

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