Metabolomic Profiling of Arginine Metabolome Links Altered Methylation to Chronic Kidney Disease Accelerated Atherosclerosis

Journal of Proteomics & Bioinformatics
Anna V MathewSubramaniam Pennathur

Abstract

Atherosclerotic cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD), but the mechanisms underlying vascular disease has not been fully understood. As the nitrogen donor in nitric oxide (NO(·)) synthesis, arginine and its metabolic products are integrally linked to vascular health and information. We hypothesized that derangements in this pathway could explain, in part, increased atherosclerotic risk in CKD. We developed a targeted metabolomic platform to profile quantitatively arginine metabolites in plasma by liquid chromatography tandem mass spectrometry (LC/MS). Male low-density lipoprotein receptor defcient (LDLr(-/-)) mice at age 6 weeks were subjected to sham or 5/6 nephrectomy surgery to induce CKD. Subsequently, the animals were maintained on high fat diet for 24 weeks. Targeted metabolomic analysis of arginine metabolites in plasma was performed by isotope dilution LC/MS including asymmetric dimethyl arginine (ADMA), symmetric dimethyl arginine (SDMA), N-mono-methylarginine (NMMA), arginine and citrulline. Although elevated plasma levels of ADMA and SDMA were found in the CKD mice, only higher ADMA level correlated with degree of atherosclerosis. No significant differences...Continue Reading

Methods Mentioned

BETA
dissection
reverse phase chromatography
tandem spectrometry

Software Mentioned

Image Pro
GraphPad Prism
Agilent Mass Hunter Analyst
SPSS

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