title: Chemical composition-oriented receptor selectivity of L5, a naturally occurring atherogenic low-density lipoprotein.
abstract: Anion-exchange chromatography resolves human plasma low-density lipoprotein (LDL) into 5 subfractions, with increasing negative surface charge in the direction of L1 to L5. Unlike the harmless L1 to L4, the exclusively atherogenic L5 is rejected by the normal LDL receptor (LDLR) but endocytosed into vascular endothelial cells through the lectin-like oxidized LDL receptor-1 (LOX-1). Analysis with SDS-PAGE and 2-dimensional electrophoresis showed that the protein framework of L1 was composed mainly of apolipoprotein (apo) B100, with an isoelectric point (pI) of 6.620. There was a progressively increased association of additional proteins, including apoE (pI 5.5), apoAI (pI 5.4), apoCIII (pI 5.1), and apo(a) (pI 5.5), from L1 to L5. LC/MSEwas used to quantify protein distribution in all subfractions. On the basis of weight percentages, L1 contained 99% apoB-100 and trace amounts of other proteins. In contrast, L5 contained 60% apoB100 and substantially increased amounts of apo(a), apoE, apoAI, and apoCIII. The compositional characteristics contribute to L5's electronegativity, rendering it unrecognizable by LDLR. LOX-1, which has a high affinity for negatively charged ligands, is known to mediate the signaling of proinflammatory cytokines. Thus, the chemical composition-oriented receptor selectivity hinders normal metabolism of L5, enhancing its atherogenicity through abnormal receptors, such as LOX-1.
authors.affiliation: Vascular and Medicinal Research, Texas Heart Institute, Houston, TX 77030, USA ; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, and Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Liang-Yin
authors.initials: LY
authors.lastname: Ke
authors.forename: David A
authors.initials: DA
authors.lastname: Engler
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lu
authors.forename: Risë K
authors.initials: RK
authors.lastname: Matsunami
authors.forename: Hua-Chen
authors.initials: HC
authors.lastname: Chan
authors.forename: Guei-Jane
authors.initials: GJ
authors.lastname: Wang
authors.forename: Chao-Yuh
authors.initials: CY
authors.lastname: Yang
authors.forename: Jan-Gowth
authors.initials: JG
authors.lastname: Chang
authors.forename: Chu-Huang
authors.initials: CH
authors.lastname: Chen
keywords: LDL receptor; LOX-1; apolipoproteins; atherosclerosis; electronegative; low-density lipoprotein