title: Electronegative low-density lipoprotein. A link between apolipoprotein B misfolding, lipoprotein aggregation and proteoglycan binding.
abstract: OBJECTIVE
  Subendothelial retention of lipoproteins is considered the first step in the development of atherosclerosis, but the molecular mechanisms involved are poorly understood. Recent findings on the atherogenic properties of a minor electronegative fraction of LDL (LDL(-)) could contribute to a better understanding of this process.
  
  
  RESULTS
  Circular dichroism, Trp-fluorescence and two-dimensional nuclear magnetic resonance have shown that apolipoprotein B (apoB) in LDL(-) has an abnormal, misfolded conformation. Immunochemical analysis revealed a different conformation, mainly in the N-terminal and C-terminal extremes. These alterations contribute to the high susceptibility to aggregation of LDL(-). Moreover, LDL(-) can seed the aggregation of native LDL, suggesting an amyloidogenic character that has been attributed to the amphipathic helix cluster in the α2-domain. A phospholipase C (PLC)-like activity associated to LDL(-) seems to play a major role in the LDL(-)-induced aggregation. The aggregation of LDL(-) increases its binding to proteoglycans because of the abnormal conformation of the N-terminal extreme of apoB.
  
  
  CONCLUSIONS
  LDL(-) could play a relevant role in atherogenesis by acting as a priming factor that stimulates lipoprotein aggregation. This process, which appears to be mediated by a PLC-like activity intrinsic to LDL(-), increases the binding of LDL to proteoglycans and could promote subendothelial retention of these lipoproteins.
authors.affiliation: Biochemistry Department, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain. jsanchezq@santpau.cat
authors.forename: José L
authors.initials: JL
authors.lastname: Sánchez-Quesada
authors.forename: Sandra
authors.initials: S
authors.lastname: Villegas
authors.forename: Jordi
authors.initials: J
authors.lastname: Ordóñez-Llanos
mesh_terms: D001055:Apolipoproteins B / Q000737:chemistry*; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology*; D002942:Circular Dichroism; D042783:Endothelial Cells / Q000737:chemistry; D004789:Enzyme Activation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008074:Lipoproteins / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D011509:Proteoglycans / Q000737:chemistry*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011509:Proteoglycans; C099252:oxidized low density lipoprotein; D010738:Type C Phospholipases