Effect of chronic treatment with acetylsalicylic acid and clopidogrel on atheroprogression and atherothrombosis in ApoE-deficient mice in vivo.
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.
Schulz
Christian
C
Deutsches Herzzentrum Muenchen and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitaet, Muenchen, Germany. schulz@dhm.mhn.de
Konrad
Ildiko
I
Sauer
Susanne
S
Orschiedt
Lena
L
Koellnberger
Maria
M
Lorenz
Reinhard
R
Walter
Ulrich
U
Massberg
Steffen
S
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D002791:Cholesterol, Dietary; D000077144:Clopidogrel; D004195:Disease Models, Animal; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012421:Rupture; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin