Metabolomics & Atherosclerosis

Author

CHENG KIAN KAI/UNIVERSITY OF CAMBRIDGE, UNITED KINGDOM.

Language

English

Title

Metabolomics & Atherosclerosis

Proceeding

7th INTRACOM – 2nd ICBWI 2009

Date

24th July 2009

Place Held

PWTC, Kuala Lumpur

Abstract

Atherosclerosis is a process of progressive arterial wall thickening, and is the main cause of death in Westernized countries. It is a complex process often initiated by hypercholesterolemia, and has been associated with risk factors such as elevated blood cholesterol concentration, a high fat diet, low concentrations of antioxidants in blood plasma, and smoking. In addition to these conventional atherosclerotic risk factors, recent studies have suggested roles for small molecule metabolites in the development and treatment of atherosclerosis. Homocysteine has been recognized as an independent risk factor of atherosclerosis; and betaine supplementation has been used to reduce its concentration in blood. In addition, taurine supplementation was found to reduce the concentration of blood cholesterol, and retards arterial lipid accumulation in various animal models. In humans, a strong and inverse association between taurine excretion and mortality from ischemic heart disease has been previously reported [1].


Most mouse strains are naturally resistant to atherosclerosis, although the C57BL/6 strain is susceptible to diet-induced atherosclerosis. Since the introduction of recombinant technology, a number of mouse models have been developed to investigate atherosclerosis including the apolipoprotein E gene knockout mouse and the low density lipoprotein receptor knockout (LDLR-/-) mouse. In this study, we have used 1H nuclear magnetic resonance (NMR) spectroscopy to examine the blood plasma and urinary metabolic profiles of the LDLR-/- mice. Consistent with previous studies, these mice developed hypercholesterolemia and atherosclerosis when fed a high fat/cholesterol diet. In addition, multivariate statistics of the metabolomic data highlighted significant changes in the tricarboxylic acid cycle and fatty acid metabolism, as a result of the high fat/cholesterol diet. Furthermore, our metabolomic study demonstrates that the effect of the high fat/cholesterol diet, LDL receptor gene deficiency, and the diet-genotype interaction caused a significant perturbation in the choline metabolism, particularly the choline oxidation pathway. This study suggests that metabolites in urine and blood plasma could be used to monitor atherosclerosis onset and drug efficacy during treatment.

Keywords

Metabolomics, Atherosclerosis

Session

Symposium 2C (ICBWI)

Topic

Biomolecule Discovery