Effect of chronic treatment with acetylsalicylic acid and clopidogrel on atheroprogression and atherothrombosis in ApoE-deficient mice in vivo

Thromb Haemost. 2008 Jan;99(1):190-5. doi: 10.1160/TH07-03-0235.

Abstract

Acetylsalicylic acid (ASA) and the thienopyridine clopidogrel are established anti-platelet drugs that significantly reduce secondary cardiovascular events in patients with manifest atherosclerosis. However, their impact on atherosclerotic lesion development remains controversial. Four-week-old ApoE-deficient mice were randomly assigned to four groups receiving a cholesterol diet together with either ASA (5 mg/kg), or clopidogrel (25 mg/kg), or a combination of both ASA and clopidogrel, or vehicle for 8-12 weeks. Using intravital microscopy we found that daily administration of ASA in combination with clopidogrel reduces platelet thrombus formation following rupture of atherosclerotic plaque in vivo by approximately 50%. However, therapy with ASA or clopidogrel alone, or in combination for a period of 8-12 weeks had no significant effect on adhesion of platelets to dysfunctional endothelial cells or on atherosclerotic lesion formation in the aortic root or the carotid artery. In conclusion, anti-platelet therapy is effective in reducing platelet adhesion and subsequent thrombus formation following rupture of atherosclerotic plaque in vivo. However, our data do not support a role of either drug in the primary prevention of atherosclerosis in ApoE-deficient mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Aspirin / administration & dosage
  • Aspirin / pharmacology*
  • Atherosclerosis / blood
  • Atherosclerosis / complications
  • Atherosclerosis / etiology
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Carotid Arteries / drug effects
  • Carotid Arteries / metabolism
  • Cholesterol, Dietary
  • Clopidogrel
  • Disease Models, Animal
  • Disease Progression
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Microscopy, Video
  • Platelet Adhesiveness / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology*
  • Rupture
  • Thrombosis / blood
  • Thrombosis / etiology
  • Thrombosis / pathology
  • Thrombosis / prevention & control*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology
  • Time Factors

Substances

  • Apolipoproteins E
  • Cholesterol, Dietary
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Aspirin