Abstract
BackgroundThe endothelium is a key variable in the pathogenesis of atherosclerosis and its complications, particularly coronary artery disease (CAD). Current evidence suggests that the endothelial status can be regarded as an integrated index of individual atherogenic and anti-atherogenic properties, and that the interaction between circulating factors and the arterial wall might be critical for atherogenesis. In organism-level investigations, a functional view is provided by metabolomics, the study of the metabolic profile of small molecules. We sought to verify whether metabolomic analysis can reveal the presence of coronary microenvironment peculiarities associated with distinct manifestations of CAD.MethodsThirty-two coronary blood samples were analyzed using 1H-NMR-based metabolomics. Samples collected from patients with evidence of myocardial ischemia formed the case group, and were further divided into the stenotic-disease (SD) group (N = 13) and absence of stenosis (microvascular disease; “Micro”) group (N = 8); specimens of patients presenting no evidence of ischemic heart disease (dilated cardiomyopathy, valvular diseases) constituted the control group (N = 11).ResultsApplication of an orthogonal partial least squares discriminant analysis (OPLS-DA) model to the entire dataset clearly separated the samples into 3 groups, indicating 3 distinct metabolic fingerprints. Relative to control-group members, Micro patients showed a higher content of 2-hydroxybutirate, alanine, leucine, isoleucine, and N-acetyl groups and lower levels of creatine/phosphocreatine, creatinine, and glucose, whereas SD patients showed higher levels of 3-hydroxybutirate and acetate and a lower content of 2-hydroxybutirate. Moreover, relative to SD patients, Micro patients showed higher levels of 2-hydroxybutirate, alanine, leucine, and N-acetyl groups and lower levels of 3-hydroxybutirate and acetate.ConclusionsSpecific coronary microenvironments are likely associated with distinct development and pathological expression of CAD.
Highlights
The endothelium is a key variable in the pathogenesis of atherosclerosis and its complications, coronary artery disease (CAD)
Atherosclerosis is currently the leading cause of death and disability in developing countries and is mainly expressed in the form of coronary artery disease (CAD), which is associated with high morbidity and mortality [1, 2]
We consecutively enrolled patients requiring coronary angiography among those screened in our clinic; they were informed of the purpose and methodology of the study and their written consent was obtained prior to inclusion
Summary
The endothelium is a key variable in the pathogenesis of atherosclerosis and its complications, coronary artery disease (CAD). Systemic cardiovascular risk factors for atherosclerosis (hyperlipidemia, diabetes mellitus, smoking and hypertension) have been identified [3,4,5,6,7,8,9], a wide series of researches suggest that the local microenvironment, that comprehends arterial mechanics, matrix remodelling and lipid deposition, plays a key role in regulating the susceptibility to plaque development and progression, regulating the function of endothelial cells These microenvironmental stimuli are capable of modulate other aspects of the microenvironment through collective adaptation [10]. By combining targeted and non-targeted approaches, metabolomic analysis has identified small-molecule metabolite profiles of diverse cardiovascular risk factors and diseases [11,12,13]
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