Coronary artery in-stent stenosis persists despite inhibition of the von Willebrand factor--collagen interaction in baboons.
Revascularization techniques, such as angioplasty and stent implantation, frequently lead to restenosis due to the formation of neointima after platelet activation and the concomitant release of various smooth muscle cell mitogenic and attractant factors. We here investigate whether inhibition of initial platelet adhesion after stent implantation can decrease neointima formation in a clinically relevant baboon model of in-stent stenosis using standard treatment with aspirin, clopidogrel and heparin. Inhibition of platelet adhesion was established by administration of the anti-von Willebrand factor (VWF) monoclonal antibody 82D6A3, which inhibits VWF binding to collagen. Administration of 82D6A3 resulted in a complete inhibition of VWF binding to collagen during the first three days after stent implantation. No thrombocytopenia or prolongation of the bleeding time was observed. Our results show that the formation of neointima was not affected in the group of baboons where primary platelet adhesion was abolished with 82D6A3 when compared to the control group. Vascular injury scores were the same in both groups. Inhibition of platelet adhesion during the first three days after stenting, on top of standard treatment with aspirin, clopidogrel and heparin, had no effect on neo-intima formation in a baboon model of in-stent stenosis. During the last decade, attempts to translate seemingly effective therapies based on smaller animal experimentation to the clinic have consistently failed. This study, using a non-human primate model that more closely resembles the clinical situation, presents a model that may be of further clinical interest for studying the prevention of restenosis.
De Meyer
Simon F
SF
Laboratory for Thrombosis Research, I.R.C., KULeuven Campus Kortrijk, E. Sabbelaan 53, 8500 Kortrijk, Belgium.
Staelens
Stephanie
S
Badenhorst
Philip N
PN
Pieters
Henry
H
Lamprecht
Seb
S
Roodt
Jan
J
Janssens
Stefan
S
Meiring
Muriel
M
Vanhoorelbeke
Karen
K
Bruwer
André
A
Brown
Stephen
S
Deckmyn
Hans
H
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000295:instrumentation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000494:pharmacology; D000077144:Clopidogrel; D003094:Collagen / Q000378:metabolism*; D023921:Coronary Stenosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006493:Heparin / Q000494:pharmacology; D008297:Male; D048549:Papio ursinus; D010973:Platelet Adhesiveness / Q000187:drug effects*; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D014841:von Willebrand Factor; D006493:Heparin; D003094:Collagen; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin