Metabolics and Cardiovascular Disease

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. Metabolomics The science of metabolomics is the systematic study of the "unique chemical fingerprints of small molecules or metabolite profiles that are related to a variety of cellular metabolic processes in a cell, organ, or organism" (Senn, et al., 2012).

The creation of metabolic profiles enables direct and indirect insights into the detectable physiology of a broad range of biospecimens (Senn, et al., 2012). Metabolic profiling provides information that exceeds what is made available through processes that, for instance, provide messenger RNA gene expression data and proteomic analyses (Senn, et al., 2012). Metabolics have been used in both "open" and "closed" profiles. Raw data is the product of open profiling as the analysis is untargeted (Senn, et al., 2012).

While the untargeted approach can lead to the discovery of new or previously unrecognized disease processes, the lack of specificity may contribute to difficulties in efforts to understand disease pathways (Senn, et al., 2012). Because of this difficulty, some experts assert that, "the patterns may just be noise rather than signal" (Senn, et al., 2012, p, 72). Alternately, closed or targeted analysis focuses on a limited set of metabolites, which results in more purposeful examinations (Senn, et al., 2012).

The significance of targeted profiling is that it enables the validation of a biomarker following its discovery (Senn, et al., 2012). Because the precise metabolites are known and detectable, closed profiling fosters greater understanding of the disease, as well as the reproducibility of the underlying disease process (Senn, et al., 2012). 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.