Prolonged clopidogrel application reduces tissue factor expression after percutaneous coronary intervention in the porcine model.
BACKGROUND
Late thrombotic events are important complications associated with intracoronary brachytherapy (ICBT) using ionizing radiation (IR) or with antiproliferative treatment modalities such as drug-eluting stents (DES). The mechanism mediating these thrombotic events is not well understood. This study assessed the effect of prolonged clopidogrel treatment on tissue factor (TF) expression in coronary arteries and on the circulating TF level after percutaneous transluminal coronary angioplasty /ICBT in a porcine coronary model.


METHODS
Pigs were treated with aspirin plus a 300 mg loading dose of clopidogrel one day before percutaneous coronary intervention (PCI), followed by a daily dose of clopidogrel and aspirin. During PCI one of the two balloon-injured arteries was treated by brachytherapy. Animals were sacrificed at different time points. The pigs, which were sacrificed 3 months post-PCI, were divided into two groups (Group I: clopidogrel for 3 months; Group II: clopidogrel for 1 month). Plasma TF was measured by enzyme-linked immunosorbent assay in blood samples taken from all pigs before and immediately after intervention and before sacrifice. Morphometric analysis was performed on digitalized images employing the software LUCIA G for TF staining. Vascular TF expression levels were assessed by quantitative real-time polymerase chain reaction.


RESULTS
Prolonged clopidogrel application significantly reduced coronary TF at the protein (Group I vs. II, 8.975 ± 3.947% vs. 26.44 ± 5.375%, P = .007) and mRNA level [Group I vs. II, (0.3501 ± 0.0519) × 10(-3) vs. (0.7073 ± 0.0436) × 10(-3), P<.0005]. Circulating TF protein tended to be lower after 3 months than after 1 month clopidogrel treatment post-PCI (Group I vs. Group II, 488.3 ± 35.37 pg/ml vs. 572.3 ± 39.9 pg/ml, P = .130).


CONCLUSIONS
Prolonged clopidogrel treatment reduced coronary TF expression and tended to reduce the blood TF level post-PCI, thus possibly modulating the risk of late thrombosis.
Department of Cardiology and Pneumonology, Medical Clinic II, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Yunus
Y
Ayral
Ursula
U
Rauch
Petra
P
Goldin-Lang
Andreas
A
Eisenreich
Wojciech
W
Pepke
Carolin
C
Deiner
Peter L
PL
Schwimmbeck
Heinz-Peter
HP
Schultheiss
Klaus
K
Pels
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage; D001918:Brachytherapy / Q000009:adverse effects; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D007150:Immunohistochemistry; D023421:Models, Animal; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D034421:Sus scrofa; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D015854:Up-Regulation
D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D005337:Fibrin; D005340:Fibrinogen; D013925:Thromboplastin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin