Summary
Revascularization techniques, such as angioplasty and stent implantation, frequently
lead to restenosis due to the formation of neointima after platelet activation and
the concomittant 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.
Keywords
vonWillebrand factor - stenosis - baboon model - stent - neointima
