Mass spectrometry and metabolomics for cardiovascular disease biomarkers

Mass Spectrometry in Medical Research

Metabolics is an emerging approach to cardiovascular biomarker research. Through the use of metabolic approaches based on chemistry, the metabolic properties that underlie a variety of cardiovascular disease (CVD) states can be analyzed (Senn, et al., 2012). Biomarkers are currently identified in biospecimens according to quantified protein-based end products, rather than representing the disease states by the metabolomics profiles that characterize the disease (Senn, et al., 2012). The literature shows use of both open (unbiased) and closed (targeted) approaches to "identifying, describing, and verifying metabolic differences between disease and nondisease conditions" (Senn, et al., 2012). The use of metabolomics profiling, without evidence of traditional risk factors, is being used to learn more about mortality due to cardiovascular disease, as well as myocardial infarction and stroke (Senn, et al., 2012).

Cardiovascular disease (4-6 sentences are enough)

The leading cause of mortality and morbidity in developed nations is cardiovascular disease (CVD) (Barallobre-Barreiro, et al., 2013). The current state of cardiovascular medicine requires reliance on commonly known and quite well understood conventional risk factors: Age, diabetes, gender, hypertension, and smoking (Barallobre-Barreiro, et al., 2013). A considerable difficulty associated with these risk factors is their prevalence in the general population, which results in high prediction failure rates for a majority of CVD cases over a 10-year period; this is true with even the best available algorithms for acute coronary events (Barallobre-Barreiro, et al., 2013). Moreover, the expanse of genetic backgrounds of people with CDV, the pathological stages and etiologies of heart failure, for instance, are numerous (Barallobre-Barreiro, et al., 2013). The current use of biomarker assessment is based on quantification of a handful of metabolites or proteins.

Mass Spectrometry-based Metabolomics

Mass spectrometry distinguishes metabolites through the use of mass / charge (m/z). A very large array of metabolites can be analyzed with enhanced sensitivity by using a combination of mass spectrometry and various methods of separation. Generally, two primary approaches are used for metabolite separation: 1) Gas chromatography, which has particular utility with volatile, nonpolar metabolites; and, 2) liquid chromatography, which is used for nonvolatile metabolites in solution. The techniques used in mass spectrometry are more sensitive than approaches based in nuclear magnetic resonance, a distinction that means more metabolite peaks can be quantified through mass spectrometry. Accordingly, liquid chromatography (LC-MS) and gas chromatography (GC-MS) are used to resolve the small quantities of compounds present, which then fosters the identification and quantification to a degree that extends into the attomole to picomole / liter range.

Identification of a Novel Biomarker for CVD

Technological advancements in metabolic tools have enabled the measurement of low-molecular-weight metabolics in biospecimens (Senn, et al., 2012). For instance, nuclear magnetic resonance spectroscopy and mass spectrometry, coupled with increasingly sophisticated bioinformatics and analytical tools, are providing unique insights into both established and novel metabolic pathways (Senn, et al., 2012). The use of metabolics in the study of cardiovascular biomarkers is of particular interest as metaboloics may be translated to cardiovascular biomarkers (Senn, et al., 2012). Indeed, in what is considered a conventional trajectory for biomarker discovery, progress in translating metabolics to cardiovascular biomarkers has followed the pattern of identification to confirmation to clinical validation to bedside testing (Senn, et al., 2012). Systemic metabolics offers promise in physiologic understanding of cardiovascular disease states beyond that provided by traditional profiling (Senn, et al., 2012). The research looks toward the translation of metabolics to cardiovascular biomarkers that may enable the generation of descriptions of individual and population responses to therapeutic interventions or to relevant exposures from the environment (Senn, et al., 2012).

At the most fundamental level, metabolite biomarkers may be combined with clinical variables, genetics, and other biomarkers in order to advance the models designed for diagnosis or risk prediction (Shah, et al., 2015). In genetic research, metabolites can serve as phenotypes and, in a systems biology approach, metabolites can be integrated with multiple omic platform analysis (Shah, et al., 2015). The aim of a systems biology approach is to create a global map that shows all the functional relationships and interactions of all the physical elements in the cell, including genes, metabolites, proteins, and the like; this serves as a roadmap for the manner in which physiological homeostasis is affected by the interactions of the different relevant tissues and organ systems (Shah, et al., 2015). Mass Spectrometry-based Metabolomics hold promise for the a novel biomarker for early identification of individuals at risk for future cardiovascular events to allow for effective therapy and increase the chance of survival.