Riitta Lassila
Helsinki University Hospital, Finland
Title: Locally acting antiplatelet and anticoagulant APAC, a mimic of heparin proteoglycan, inhibits acute ischemic kidney injury
Biography
Biography: Riitta Lassila
Abstract
APACs are unique dual antiplatelet and anticoagulant molecules, which mimic the vascular tissue residing mast cell heparin proteoglycans. Platelet activation and interaction with vascular wall with ensuing coagulation are important pathogenic mechanisms underlying various diseases, including kidney disease. We have shown that in ANCA-vasculitis kidney function is associated with strong coagulation activity during the acute phase, and that vascular access problems are prevalent in dialysis patients with coagulation abnormalities or thrombophilias. We have studied our potent, naturally occurring, locally acting antithrombotic in prevention of ischemic short- and long-term reversible or irreversible kidney injuries.
APACs show strong inhibition of collagen-induced platelet aggregation and procoagulant activity in association with vascular damage. In various animal models we have shown that APAC is able to target vascular injury site from the circulation and upon local application, having a long vascular retention time. Being highly negatively charged large molecules (MW 200-400 kDa) APACs interact avidly with vascular von Willebrand factor, laminin and collagen, whereas PECAM and podocalyxin positive vascular sites fail to colocalize with APAC. When infused intravenously 10 min prior to arterial clamping APAC protected kidneys from ischemic reperfusion injury, assessed both by clinical and laboratory or pathology findings. Intriguingly, in severe irreversible injury of 60 min ischemia time, APAC provided renoprotection. We are currently working with a diabetic nephropathy mouse model to study the possible role of APAC in the development of streptozotocin-induced diabetes and kidney damage.