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

Abstract

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.

Simultaneous Determination of 6 l-Arginine Metabolites in Human and Mouse Plasma by Using Hydrophilic-Interaction Chromatography and Electrospray Tandem Mass Spectrometry

“…Several studies have suggested that increased systemic inflammation is associated with impaired arginine metabolism (31–34). We therefore conducted two separate sets of experiments in both humans and mice to determine whether we could use this method to test the hypothesis that increased systemic inflammation alters flux through arginine metabolic pathways by decreasing bioavailability of arginine and its amino acid metabolites, and increasing the concentration of methylated arginines.…”

Endothelial dysfunction, ADMA and insulin resistance in essential hypertension

“…On the other hand, endothelial dysfunction, by itself, worsens IR by altering transcapillary passage of insulin to target tissues, establishing a reverberating cycle that, if not interrupted, leads to the progression of vascular damage. ADMA has been identified as an independent predictor of morbidity and mortality in different setting of patients [6][7][8][9]27], probably because it reduces NO bioavailability [28], promotes inflammatory processes and the increase of acute phase inflammatory response proteins, as CRP [29], and interacts with the latter in affecting insulin sensitivity [30]. In confirmation of this, elevated ADMA levels have been documented in different clinical conditions as dyslipidemia [3], high BP [9], diabetes [4], hyperhomocysteinemia [5], and renal failure [2,6,7], all associated with endothelial dysfunction.…”

Effects of Rosuvastatin on Asymmetric Dimethylarginine Levels and Early Atrial Fibrillation Recurrence after Electrical Cardioversion

“…One interesting finding in the present study is that rosuvastatin treatment can significantly decrease serum ADMA levels in patients without AF recurrence, but not in patients with AF recurrence, which was probably due to the shorter treatment period of rosuvastatin in these subjects. There are now compelling data that ADMA is a biomarker for the progression of cardiovascular disease and there are some data emerging that ADMA, as a possible mediator, may be functionally important in many heart diseases 14 . ADMA leads to nitric oxide (NO) deficiency in many clinical settings by inhibiting all three NOS isoforms.…”