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

• Published in: European journal of vascular and endovascular surgery Vol. 58; no. 6; pp. 903 - 911
• Main Authors: Barreiro, Karina A., Tulamo, Riikka, Jouppila, Annukka, Albäck, Anders, Lassila, Riitta
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01-12-2019
• Subjects: Anastomosis, Surgical - adverse effects; Angioplasty, Balloon - adverse effects; Animals; Anticoagulants - administration & dosage; APAC; Arteriovenous fistula; Balloon angioplasty; Disease Models, Animal; Drug Combinations; Endothelium, Vascular - drug effects; Endothelium, Vascular - pathology; Female; Femoral Artery - drug effects; Femoral Artery - pathology; Femoral Artery - surgery; Femoral Vein - drug effects; Femoral Vein - pathology; Femoral Vein - surgery; Humans; Iliac Artery - drug effects; Iliac Artery - injuries; Iliac Artery - surgery; Laminin - metabolism; Platelet Aggregation Inhibitors - administration & dosage; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Porcine vascular injury model; Sialoglycoproteins - metabolism; Sus scrofa; Thrombosis - etiology; Thrombosis - prevention & control; Vascular System Injuries - complications; Vascular System Injuries - drug therapy; Von Willebrand factor; von Willebrand Factor - metabolism; Balloon angioplasty; Porcine vascular injury model; Arteriovenous fistula; Von Willebrand factor; APAC
• ISSN: 1078-5884; 1532-2165
• DOI: 10.1016/j.ejvs.2019.05.019

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) in vivo iliac and carotid artery balloon angioplasty injury, and 3) in vitro femoral artery endothelial denudation injury. Biotinylated APAC (0.5 mg/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 in vivo and in vitro 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.