L-4F alters hyperlipidemic (but not healthy) mouse plasma to reduce platelet aggregation.

Academic Article

Abstract

  • UNLABELLED: Background and Purpose- Hyperlipidemia is associated with platelet hyperreactivity. We hypothesized that L-4F, an apolipoprotein A-I mimetic peptide, would inhibit platelet aggregation in hyperlipidemic mice. METHODS AND RESULTS: Injecting L-4F into apolipoprotein E (apoE)-null and low-density lipoprotein receptor-null mice resulted in a significant reduction in platelet aggregation in response to agonists; however, there was no reduction in platelet aggregation after injection of L-4F into wild-type (WT) mice. Consistent with these results, injection of L-4F into apoE-null mice prolonged bleeding time; the same result was not found in WT mice. Incubating L-4F in vitro with apoE-null platelet-rich plasma also resulted in decreased platelet aggregation. However, incubating washed platelets from either apoE-null or WT mice with L-4F did not alter aggregation. Compared with WT mice, unstimulated platelets from apoE-null mice contained significantly more 12-hydroxy 5,8,10,14-eicosatetraenoic acid, thromboxane A(2), and prostaglandins D(2) and E(2). In response to agonists, platelets from L-4F-treated apoE-null mice formed significantly less thromboxane A(2), prostaglandins D(2) and E(2), and 12-hydroxy 5,8,10,14-eicosatetraenoic acid. CONCLUSIONS: By binding plasma-oxidized lipids that cause platelet hyperreactivity in hyperlipidemic mice, L-4F decreases platelet aggregation.
  • Keywords

  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid, Adenosine Diphosphate, Animals, Apolipoprotein A-I, Apolipoproteins E, Arachidonic Acid, Blood Coagulation, Collagen, Dinoprostone, Disease Models, Animal, Hyperlipidemias, Injections, Subcutaneous, Mice, Mice, Inbred C57BL, Mice, Knockout, Molecular Mimicry, Peptides, Platelet Aggregation, Platelet Aggregation Inhibitors, Platelet Function Tests, Prostaglandin D2, Receptors, LDL, Thromboxane A2
  • Digital Object Identifier (doi)

    Authorlist

  • Buga GM; Navab M; Imaizumi S; Reddy ST; Yekta B; Hough G; Chanslor S; Anantharamaiah GM; Fogelman AM
  • Start Page

  • 283
  • End Page

  • 289
  • Volume

  • 30
  • Issue

  • 2