Metabolomic Approach to Redox and Nitrosative Reactions in Cardiovascular Diseases

Abstract

Metabolomics, also referred to as metabonomics, is one of the most recent innovative technologies in medicine. It offers a direct functional read-out of phenotypes by the detection, identification, and quantification of a large number of metabolites within a biological sample such as urine and blood. Metabolites (<1500 Da) represent the output of cellular metabolism, accounting for expression and activity of genes, transcripts, and proteins, and offering unique insights into small molecule regulation, which may uncover new biochemical patterns. Metabolomics research has considerable potential for translating the metabolic fingerprint into personalized therapeutic strategies. Within the field of interest, cardiovascular disease (CVD) is one of the most developed areas. However, CVD remains the leading cause of death worldwide with a marked increase in mortality rates over the past six decades. In this scenario, recent findings indicate the important role of redox and nitrosative (RN) reactions in CVD development and progression. RN reactions are generally involved in the homeostatic modulation of a wide number of cellular and organ functions. Conversely, the imbalance of these reactions may lead to a condition of allostasis that in turn can cause CVD. The aim of this review is to highlight how the use of metabolomics may be useful for the study of RN reactions related to CVD, providing a tool to understand the mechanisms underlying reactions that could lead to impaired ROS or RNS formation.

Keywords: cardiovascular diseases; metabolomics; nitric oxide; reactive oxygen species; redox and nitrosative reactions.

FIGURE 1

NO synthesis through the NADPH and tetrahydrobiopterin-dependent oxidation of the amino acid L-arginine to L-citrulline by NO synthases. AL, argininosuccinate lyase; Arg, arginase; AS, argininosuccinate synthetase; BH4, tetrahydrobiopterin; NOS, NO synthases; OTC, ornithine transcarbamylase.