Coronary blood metabolomics fingerprint differentiates healthy subjects from patients with stenosing or microvascular ischemic disease

Background. Endothelium is a key variable in the pathogenesis of atherosclerosis and its complications, particularly coronary artery disease (CAD). Current evidence suggests that endothelial status may be regarded as an integrated index of individual atherogenic and atheroprotective factors. Therefore, interplay between circulating factors and properties of the local endothelium may be critical for the development of atherosclerosis. Metabolomics (MBS) is the study of the metabolic profile of small molecules and provides a functional view of the studied organism. Objectives: to verify whether MBS was capable to detect the presence of differences in coronary microenvironment associated to different manifestations of CAD Methods. A 1H-NMR based MBS analysis was performed on coronary blood samples of 23 patients with indication to coronary angiography; those with evidence of myocardial ischemia formed the case group, further divided into stenotic disease (SD group; N = 13) and absence of stenosis (microvascular disease-Micro Group; N = 5 ), while those with no evidence of ischemic heart disease (dilated cardiomyopathy, valvular diseases) constituted the control group (N=5). Results. An OPLS-DA model was applied to the whole dataset. Samples are clearly separated into the three groups, indicating 3 different metabolic fingerprints. In comparison with Controls, Micro patients showed a higher content of 2-hydroxybutirate, alanine, leucine, isoleucine, N-acetygroups, and a lower content of creatine/phosphocreatine, creatinine and glucose, whereas SD patients were characterized by higher levels of 3-hydroxybutirate, acetate and a lower content of 2-hydroxybutirate. Finally, Micro patients compared to SD Group showed a higher content of 2-hydroxybutirate, alanine, leucine, N-acetygroups, and a lower content of 3-hydroxybutirate and acetate. Conclusions. Our findings seem to suggest that specific coronary microenvironments are associated with different development and pathological expression of atherosclerotic disease, as resulted by the interact of pre-determined characteristics of endothelial cells (i.g. genetic, epigenetic) with cardiovascular risk factors.