Apolipoprotein B100 danger-associated signal 1 (ApoBDS-1) triggers platelet activation and boosts platelet-leukocyte proinflammatory responses

Thromb Haemost. 2014 Aug;112(2):332-41. doi: 10.1160/TH13-12-1026. Epub 2014 May 8.


Low-density lipoproteins (LDL), occurring in vivo in both their native and oxidative form, modulate platelet function and thereby contribute to atherothrombosis. We recently identified and demonstrated that 'ApoB100 danger-associated signal 1' (ApoBDS-1), a native peptide derived from Apolipoprotein B-100 (ApoB100) of LDL, induces inflammatory responses in innate immune cells. Platelets are critically involved in the development as well as in the lethal consequences of atherothrombotic diseases, but whether ApoBDS-1 has also an impact on platelet function is unknown. In this study we examined the effect of ApoBDS-1 on human platelet function and platelet-leukocyte interactions in vitro. Stimulation with ApoBDS-1 induced platelet activation, degranulation, adhesion and release of proinflammatory cytokines. ApoBDS-1-stimulated platelets triggered innate immune responses by augmenting leukocyte activation, adhesion and transmigration to/through activated HUVEC monolayers, under flow conditions. These platelet-activating effects were sequence-specific, and stimulation of platelets with ApoBDS-1 activated intracellular signalling pathways, including Ca2+, PI3K/Akt, PLC, and p38- and ERK-MAPK. Moreover, our data indicates that ApoBDS-1-induced platelet activation is partially dependent of positive feedback from ADP on P2Y1 and P2Y12, and TxA2. In conclusion, we demonstrate that ApoBDS-1 is an effective platelet agonist, boosting platelet-leukocyte's proinflammatory responses, and potentially contributing to the multifaceted inflammatory-promoting effects of LDL in the pathogenesis of atherothrombosis.

Keywords: ApoB; LDL; Platelets; and atherosclerosis; inflammation.

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adult
  • Apolipoprotein B-100 / immunology
  • Apolipoprotein B-100 / metabolism*
  • Blood Platelets / immunology
  • Blood Platelets / metabolism*
  • Cell Communication*
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Human Umbilical Vein Endothelial Cells / immunology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Immunity, Innate
  • Inflammation / blood
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism*
  • Leukocytes / immunology
  • Leukocytes / metabolism*
  • Platelet Activation*
  • Platelet Adhesiveness
  • Receptors, Purinergic P2Y12 / metabolism
  • Signal Transduction
  • Thromboxane A2 / metabolism
  • Time Factors
  • Young Adult


  • APOB protein, human
  • Apolipoprotein B-100
  • Cytokines
  • Inflammation Mediators
  • P2RY12 protein, human
  • Receptors, Purinergic P2Y12
  • Thromboxane A2
  • Adenosine Diphosphate