An Optimized MRM-Based Workflow of the l-Arginine/Nitric Oxide Pathway Metabolites Revealed Disease- and Sex-Related Differences in the Cardiovascular Field

Abstract

Clinical data indicate that low circulating l-homoarginine (HArg) concentrations are associated with cardiovascular (CV) disease, CV mortality, and all-cause mortality. A high number of LC-based analytical methods for the quantification of HArg, in combination with the l-arginine (Arg)-related pathway metabolites, have been reported. However, these methods usually consider a limited panel of analytes. Thus, in order to achieve a comprehensive picture of the Arg metabolism, we described an improved targeted metabolomic approach based on a multiple reaction monitoring (MRM) mass spectrometry method for the simultaneous quantification of the Arg/nitric oxide (NO) pathway metabolites. This methodology was then employed to quantify the plasma concentrations of these analytes in a cohort of individuals with different grades/types of coronary artery disease (CAD) in order to increase knowledge about the role of HArg and its associated metabolites in the CV field. Our results showed that the MRM method here implemented is suitable for the simultaneous assessment of a wide panel of amino acids involved in the Arg/NO metabolic pathway in plasma samples from patients with CV disease. Further, our findings highlighted an impairment of the Arg/NO metabolic pathway, and suggest a sex-dependent regulation of this metabolic route.

Interaction of asymmetric dimethylarginine, troponin I level, and diabetes mellitus 2 type severity in patients with acute myocardial infarction

“…ADMA is a metabolite of arginine, the determination of which is useful to evaluate cardiovascular disease, kidney disease, and nonalcoholic fatty liver disease 34 . The increased concentration of ADMA in the blood plasma is connected to the increased risk of mortality and unacceptable cerebrovascular diseases, as is especially evident in the case of AMI [35][36][37][38][39][40] . In AMI, the necrotic death of cardiomyocytes occurs, characterized by the rupturing of the sarcolemma in response to a critical level of energy depletion after more than 15 minutes of ischemia.…”