A 1H NMR based metabonomics approach to progression of coronary atherosclerosis in a rabbit model

Subtle metabolic variations precede and accompany oxidative and vascular damage, which correspond to the pathophysiological process of coronary heart disease (CHD). To investigate the progression of coronary atherosclerosis and identify potential biomarkers, the metabolic profiling in the plasma of rabbits fed a high-cholesterol diet were investigated using proton nuclear magnetic resonance spectroscopy (1H NMR) coupled with multivariate data analysis. Metabolite variations during atherogenesis showed a time-dependent development from physiological to pathophysiological status in rabbits. NMR-based plasma profiling demonstrated that low-density lipoprotein/very-low-density lipoprotein (LDL/VLDL), glutamine, phosphorylcholine, N-acetyl glycoproteins, betaine, proline, and tyrosine were the most positively corresponded metabolites of the aortic atherosclerotic lesions, whereas high-density lipoprotein (HDL), unsaturated lipids, citrate, glucose, and creatinine were the most negatively correlated metabolites. Multiple biochemical changes indicated dyslipidemia, oxidative stress, alteration of energy metabolism, and endothelial dysfunction after cholesterol overloading, and subsequently to early coronary atherosclerosis in rabbits. This study indicated that 1H NMR based metabonomics can provide valuable information for the investigation of the dynamic biochemical variations underlying complex physiopathological conditions. It also offers a promising non-invasive means to the discovery of biomarkers for monitoring the onset and progression of CHD.