Inhibition of platelet aggregation ex vivo is repressed in apolipoprotein E deficient mice

Can J Physiol Pharmacol. 2017 Aug;95(8):954-960. doi: 10.1139/cjpp-2017-0314. Epub 2017 Jul 13.


In the present study, we assessed whether the endogenous platelet inhibitory mechanisms are altered in the early to moderate stages of the atherosclerotic process. Apolipoprotein E deficient mice (ApoE-/-), a mouse model of atherosclerosis, and their wild-type (WT) counterparts were used to assess agonist-stimulated synthesis of prostacyclin (PGI2), inhibition of platelet aggregation ex vivo, and intra-platelet cAMP levels. Basal U46619 and ADP -induced platelet aggregation in vitro were increased in ApoE-/- mice at 18-20 weeks in comparison with 8-10 weeks of age. Systemically administered endothelin-1 (ET-1) or bradykinin (BK) inhibited platelet aggregation in a similar fashion in 8- to 10-week-old ApoE-/- and WT mice, but not in the ApoE-/- mice at 18-20 weeks of age, although both peptides maintained their capacity to increase plasma levels of the PGI2. Intravenous infusion of PGI2 also failed to inhibit platelet aggregation ex vivo in 18- to 20-week-old ApoE-/- mice. Interestingly, both BK and PGI2 retained their ability to increase intraplatelet cAMP in WT and ApoE-/- mice. Our results suggest that a loss of activity of endogenous inhibitorymechanisms could contribute to the increased platelet reactivity in ApoE-/- mice, and that this phenomenon occurs early in the intermediate stage of the atherosclerotic process.

Keywords: AMPc; atherosclerosis; athérosclérose; bradykinin; bradykinine; cAMP; endothelin-1; endothelium; endothéline-1; endothélium; mouse; plaquette; platelet; prostacyclin; prostacycline; souris.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Adenosine Diphosphate / pharmacology
  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Apolipoproteins E / deficiency*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / physiopathology
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Blood Platelets / physiology
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Epoprostenol / metabolism
  • Female
  • Foam Cells / drug effects
  • Foam Cells / pathology
  • Male
  • Mice
  • Platelet Aggregation / drug effects*


  • Apolipoproteins E
  • Adenosine Diphosphate
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Epoprostenol
  • Cyclic AMP