Electronegative low-density lipoprotein. A link between apolipoprotein B misfolding, lipoprotein aggregation and proteoglycan binding

José L. Sánchez-Quesada, Sandra Villegas, Jordi Ordóñez-Llanos

Research output: Contribution to journalReview articleResearchpeer-review

30 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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. © 2012 Wolters Kluwer Health | Lippincott Williams &Wilkins.
Original languageEnglish
Pages (from-to)479-486
JournalCurrent Opinion in Lipidology
Volume23
Issue number5
DOIs
Publication statusPublished - 1 Oct 2012

Keywords

  • apoB structure
  • LDL aggregation
  • phospholipase C
  • proteoglycans
  • sphingomyelinase

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