RESUMEN
Lipidomics, the mass spectrometry-based comprehensive analysis of lipids, has attracted attention as an analytical approach to provide novel insight into lipid metabolism and to search for biomarkers. However, an ideal method for both comprehensive and quantitative analysis of lipids has not been fully developed. Here, we have proposed a practical methodology for widely targeted quantitative lipidome analysis using supercritical fluid chromatography fast-scanning triple-quadrupole mass spectrometry (SFC/QqQMS) and theoretically calculated a comprehensive lipid multiple reaction monitoring (MRM) library. Lipid classes can be separated by SFC with a normal-phase diethylamine-bonded silica column with high resolution, high throughput, and good repeatability. Structural isomers of phospholipids can be monitored by mass spectrometric separation with fatty acyl-based MRM transitions. SFC/QqQMS analysis with an internal standard-dilution method offers quantitative information for both lipid class and individual lipid molecular species in the same lipid class. Additionally, data acquired using this method has advantages, including reduction of misidentification and acceleration of data analysis. Using the SFC/QqQMS system, alteration of plasma lipid levels in myocardial infarction-prone rabbits to the supplementation of EPA was first observed. Our developed SFC/QqQMS method represents a potentially useful tool for in-depth studies focused on complex lipid metabolism and biomarker discovery.-Takeda, H., Y. Izumi, M. Takahashi, T. Paxton, S. Tamura, T. Koike, Y. Yu, N. Kato, K. Nagase, M. Shiomi, and T. Bamba.
Asunto(s)
Cromatografía con Fluido Supercrítico , Metabolismo de los Lípidos , Espectrometría de Masas , Metabolómica/métodos , Animales , Isomerismo , Lípidos/sangre , Lípidos/química , Lípidos/aislamiento & purificación , Infarto del Miocardio/metabolismo , Conejos , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
Professor Yoshio Watanabe, who developed the WHHL rabbit, died on December 13, 2008. He had contributed to studies of lipoprotein metabolism and atherosclerosis, and to the development of hypolipidemic and/or anti-atherosclerotic compounds. WHHL rabbits show hypercholesterolemia due to deficiency of LDL receptors, and very similar lipoprotein metabolism to humans. The incidences of coronary atherosclerosis and myocardial infarction in the original WHHL rabbits were very low. After three rounds of selective breeding, the coronary plaques changed to fibroatheromas with thin fibrous caps and myocardial infarction developed spontaneously. In studies with WHHL rabbits, plaque-stabilizing effects of statins were proved. In this review, we admire his achievements and describe the history of studies using WHHL rabbits.