Abstract 513: Localised Anticoagulation Via Gene Therapy: Towards Prevention Of Cardioembolic Stroke

• DOI: 10.1161/atvb.43.suppl_1.513
• Publication Date: 2023-10-02T14:09:33Z
• Authors: Megha Kadian; Cindy Y Kok; Alexander Dupuy; Xiaoming Liu; Zoe E Clayton; Dhanya Ravindran; Renuka Rao; Emmanuel Favaloro; Jennifer L Curnow; James Chong; Freda Passam; Leonardo Pasalic; Eddy Kizana
• Keywords: Ex vivo

Introduction: The coagulation cascade thrives as the haematological gatekeeper ensuring equilibrium between blood flow and thrombosis. Under pathological conditions, positive-feedback loops compound upon one another, disrupting this increasing risk of thrombosis embolic events. Cardiac thromboembolism persists culprit behind most ischemic strokes; a majority arising from left atrial appendage. In order to combat disease overcome limitations systemic oral anticoagulants, we developed novel anticoagulant viral vector focally target cardiac regions increased thrombotic potential. Hypothesis: Our recombinant lentiviral adeno-associated vectors expressing thrombomodulin will induce significant cell autonomous effect when expressed by endothelial cells Methods: phenotype these was functionally assessed through in vitro ex vivo platforms. For testing, novel, cell-based version calibrated automated thrombogram assay, coupled with overall haemostatic potential assay were utilised determine thrombokinetics culture models. freshly isolated characterized porcine appendage used. These used endothelialise microfluidic devices, which stimulated TNF-α prior perfusion human whole blood. Changes fibrin, platelets neutrophils investigated presence absence our vectors. Results: Experimental findings work showed decrease endogenous thrombin vector-transduced cells, velocity thrombogenesis. Furthermore, transduced had marked peak rate generation increase time taken achieve generation. Conclusion: show impact inhibiting guide development focal gene therapy strategies at its point origin prevention cardioembolic-stroke.