title: Lipidomic analysis of plasma lipoprotein fractions in myocardial infarction-prone rabbits.
abstract: Lipids play important roles in the body and are transported to various tissues via lipoproteins. It is commonly assumed that alteration of lipid levels in lipoproteins leads to dyslipidemia and serious diseases such as coronary artery disease (CAD). However, lipid compositions in each lipoprotein fraction induced by lipoprotein metabolism are poorly understood. Lipidomics, which involves the comprehensive and quantitative analysis of lipids, is expected to provide valuable information regarding the pathogenic mechanism of CAD. Here, we performed a lipidomic analysis of plasma and its lipoprotein fractions in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits. In total, 172 lipids in plasma obtained from normal and WHHLMI rabbits were quantified with high throughput and accuracy using supercritical fluid chromatography hybrid quadrupole-Orbitrap mass spectrometry (SFC/Q-Orbitrap-MS). Plasma levels of each lipid class (i.e., phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, ceramide, triacylglycerol, diacylglycerol, and cholesterol ester, except for free fatty acids) in 21-month-old WHHLMI rabbits were significantly higher than those in normal rabbits. High levels of functional lipids, such as alkyl-phosphatidylcholines, phospholipids including ω-6 fatty acids, and plasmalogens, were also observed in WHHLMI rabbit plasma. In addition, high-resolution lipidomic analysis using very low density lipoprotein (VLDL) and low density lipoprotein (LDL) provided information on the specific molecular species of lipids in each lipoprotein fraction. In particular, higher levels of phosphatidylethanolamine plasmalogens were detected in LDL than in VLDL. Our lipidomics approach for plasma lipoprotein fractions will be useful for in-depth studies on the pathogenesis of CAD.
authors.affiliation: Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Institute for Experimental Animals, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan; Division of Comparative Pathophysiology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Koike
authors.affiliation: Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan; Division of Metabolomics Research, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Institute for Experimental Animals, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan; Division of Comparative Pathophysiology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiomi
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Fukusaki
authors.affiliation: Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: bamba@bioreg.kyushu-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Bamba
mesh_terms: D000818:Animals; D002518:Ceramides / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D025924:Chromatography, Supercritical Fluid; D003324:Coronary Artery Disease / Q000097:blood; D004075:Diglycerides / Q000097:blood; D005260:Female; D006949:Hyperlipidemias / Q000097:blood; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood* / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry; D008079:Lipoproteins, VLDL / Q000097:blood / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D009203:Myocardial Infarction / Q000097:blood*; D010743:Phospholipids / Q000097:blood; D011817:Rabbits; D013109:Sphingomyelins / Q000097:blood; D014280:Triglycerides / Q000097:blood
chemical_list: D002518:Ceramides; D002788:Cholesterol Esters; D004075:Diglycerides; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D010743:Phospholipids; D013109:Sphingomyelins; D014280:Triglycerides
keywords: Coronary artery disease; Lipidomics; Lipoprotein; Myocardial infarction-prone Watanabe heritable hyperlipidemic rabbit; Phosphatidylethanolamine plasmalogen; Supercritical fluid chromatography mass spectrometry