Novel Locally Acting Dual Antiplatelet and Anticoagulant (APAC) Targets Multiple Sites of Vascular Injury in an Experimental Porcine Model

Abstract

Vascular binding of dual antiplatelet and anticoagulant (APAC) was assessed in surgically created femoral arteriovenous fistula (AVF) and iliac and carotid artery injury in porcine models. Three models of collagen exposing injury were used: 1) femoral AVF, 2) invivo iliac and carotid artery balloon angioplasty injury, and 3) invitro femoral artery endothelial denudation injury. Biotinylated APAC (0.5mg/mL) was incubated with the injury site before releasing blood flow. APAC, von Willebrand factor (vWF), laminin, platelet endothelial cell adhesion molecule 1 (PECAM-1), and podocalyxin were detected in histological sections using immunofluorescence and confocal microscopy and Manders' co-localisation coefficient (M1). APAC bound to AVF at anastomosis and to both invivo and invitro injured arteries. APAC co-localised with matrix vWF (M1≥0.66) and laminin (M1≥0.60), but less so if endothelial PECAM-1 or podocalyxin was present (M1≤0.25). APAC targeted and penetrated the injured vessel wall, especially the AVF vein. APAC, compatible with its high negative charge, rapidly targets injured vessels co-localizing with matrix vWF and laminin, but not with endothelial PECAM-1 and podocalyxin. This localising feature may have potential antithrombotic implications for vascular interventions.