title: Human native, enzymatically modified and oxidized low density lipoproteins show different lipidomic pattern.
abstract: In the present paper we have performed comparative lipidomic analysis of two prototypic atherogenic LDL modifications, oxidized LDL and enzymatically modified LDL. Oxidization of LDL was carried out with different chemical modifications starting from the same native LDL preparations: (i) by copper oxidation leading to terminally oxidized LDL (oxLDL), (ii) by moderate oxidization with HOCl (HOCl LDL), (iii) by long term storage of LDL at 4°C to produce minimally modified LDL (mmLDL), or (iv) by 15-lipoxygenase, produced by a transfected fibroblast cell line (LipoxLDL). The enzymatic modification of LDL was performed by treatment of native LDL with trypsin and cholesteryl esterase (eLDL). Free cholesterol (FC) and cholesteryl esters (CE) represent the predominant lipid classes in all LDL preparations. In contrast to native LDL, which contains about two-thirds of total cholesterol as CE, enzymatic modification of LDL decreased the proportion of CE to about one-third. Free cholesterol and CE in oxLDL are reduced by their conversion to oxysterols. Oxidization of LDL preferentially influences the content of polyunsaturated phosphatidylcholine (PC) and polyunsaturated plasmalogen species, by reducing the total PC fraction in oxLDL. Concomitantly, a strong rise of the lysophosphatidylcholine (LPC) fraction can be found in oxLDL as compared to native LDL. This effect is less pronounced in eLDL. The mild oxidation of LDL with hypochlorite and/or lipoxygenase does not alter the content of the analyzed lipid classes and species in a significant manner. The lipidomic characterization of modified LDLs contributes to the better understanding their diverse cellular effects.
authors.affiliation: University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Orsó
authors.affiliation: University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Matysik
authors.affiliation: University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
authors.forename: Margot
authors.initials: M
authors.lastname: Grandl
authors.affiliation: University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.affiliation: University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. Electronic address: gerd.schmitz@klinik.uni-regensburg.de.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
mesh_terms: D001093:Arachidonate 15-Lipoxygenase / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry*; D002788:Cholesterol Esters / Q000737:chemistry*; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000302:isolation & purification; D008244:Lysophosphatidylcholines / Q000737:chemistry; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry; D010955:Plasmalogens / Q000737:chemistry; D002787:Sterol Esterase / Q000737:chemistry; D014357:Trypsin / Q000737:chemistry
chemical_list: D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010955:Plasmalogens; C099252:oxidized low density lipoprotein; C029449:polyene phosphatidylcholine; D006997:Hypochlorous Acid; D002784:Cholesterol; D001093:Arachidonate 15-Lipoxygenase; D002787:Sterol Esterase; D014357:Trypsin
keywords: Low density lipoproteins; Oxysterols; Phospholipids; eLDL; oxLDL