|
Effect of Photodynamic
Therapy on Platelet Adhesion to Vascular Adhesive Proteins
Fungaloi, Patrick1,2,3,
Statius-van Eps, Randolph2, Wu, Ya-Ping1,
Blankensteijn, Jan1, de Groot, Phillip1,
van Urk, Hero2 and LaMuraglia, Glenn3
University Hospital Utrecht, the Netherlands1
University Hospital Rotterdam, the Netherlands2
Massachusetts General Hospital, Harvard Medical School, Boston MA 021143
Abstract-
Thrombosis after vascular interventions is largely mediated by platelet
adhesion to exposed vascular adhesive components. Furthermore, activated
platelets release several mediators which may contribute to the development
of intimal hyperplasia. Photodynamic therapy (PDT) produces reactive
species that alter vascular wall biology. PDT is increasingly being
applied in the vascular surgery field to inhibit intimal hyperplasia.
In this study, the effect of PDT on platelet adhesion to treated extracellular
matrix (ECM), fibrinogen, collagen and von Willebrand Factor (vWF) was
measured. Slides covered with endothelial cell ECM, fibrinogen, collagen
or vWF were PDT-treated (photosensitizer=Photofrin, fluence 100 J/cm2,
l=630 nm) and placed in a recirculating perfusion chamber with whole
blood. Platelet adhesion was quantified by image analysis. The effect
of PDT on particular epitopes of vWF was assessed by measuring binding
of specific antibodies to treated vWF. PDT significantly decreased platelet
adhesion to the ECM (51% vs 28.6%, p=0.0004), fibrinogen (51.4% vs 23.5%,
p<0.0001) and vWF (51.5% vs 26.2%, p=0.008). However, platelet adhesion
to PDT-treated collagen was significantly increased (55.0% vs 19.8%,
p<0.0001). This increase in thrombogenicity was not witnessed on collagen
pre-incubated with vWF, which resulted in decreased platelet adhesion
(26.3% vs 15.3%, p=0.0013). Further investigation of the effects of
PDT on the vWF molecule, showed that PDT affected mostly the A1 (Gp-Ib
binding site), A2 and A3 (collagen binding site) domains of vWF, but
not the D'-D3 and B-C1 (GP-IIb/3a binding site) domains. In conclusion,
PDT can alter the extracellular matrix resulting in decreased platelet
adhesion. This reduces vascular thrombogenecity and may be a factor
in inhibiting the development of intimal hyperplasia.
Keywords: photodynamic
therapy, platelet adhesion, extracellular matrix,
proteins
|
