BS61 PIM KINASE IS A NOVEL REGULATOR OF ENDOTHELIUM-DRIVEN THROMBOSIS. Eima Karim, Amelia Drysdale, Sophie Nock, Sarah Jones, Amanda Unsworth. Manchester Metropolitan University, John Dalton Building All saints campus Manchester, LAN M15 6BH United Kingdom, UK 10.1136/heartjnl-2023-BCS.274 Atherothrombosis, the development of an occlusive clot in an artery, is triggered by atherosclerotic plaque rupture or ero- sion, and is the consequence of a complex interaction between multiple cell types in the blood and vasculature, with endothe- lial cells and platelets playing significant roles. The healthy endothelium prevents thrombosis whilst an activated or dam- aged endothelium favours thrombosis. Simultaneously targeting platelets and the endothelium could provide an effective anti- thrombotic therapeutic approach. Pim kinases (Pim-1, -2, and -3), have been shown to modu- late platelet function, and whilst shown to be expressed in endothelial cells, the role of Pim kinase in the thrombotic properties of the endothelium remains unknown. The regulatory role for Pim kinase in endothelial cell con- trol of thrombus formation in response to cigarette smoke extract (CSE) and TNFa , initiators of endothelial cell damage were therefore determined, using techniques including ELISA, immunofluorescence microscopy, qPCR, and Western Blotting. We confirmed mRNA expression of all three Pim kinase isoforms, and protein expression of Pim-1 in human umbilical vein endothelial cells (HUVECs). HUVECs treated with CSE and TNFa demonstrated a decrease in eNOS levels, a protec- tive mediator of cardiovascular homeostasis. To investigate whether Pim kinase plays a role, HUVECs were treated with AZD1208, a pan Pim kinase inhibitor, and a decrease in expression of VWF, a pro-coagulant mediator, and release of inflammatory markers, IL-6, and IL-8 were observed. Collectively, these findings identify a potential role for Pim kinase in atherothrombosis and indicates that Pim kinase inhibitors could be repurposed for use alongside other anti- thrombotic agents for the prevention of cardiovascular-related events. Conflict of Interest None BS62 ‘CARDIAC ORGANOIDS. A MODEL TO INVESTIGATE THE EFFECT OF DIABETES ON CARDIAC DEVELOPMENT AND FUNCTION’ Magdalini Eleftheriadou, Hojjat Naderi-Meshkin, Koray N Potel, Wiwit Ananda Wahyu Setyaningsih, Andrew Yacoub, Alan W Stitt, David J Grieve, Andriana Margariti. Queen's University Belfast, School of Medicine, Dentistry Queen’s University 97 Lisburn Road Belfast, ANT BT9 7BL United Kingdom, UK 10.1136/heartjnl-2023-BCS.275 Introduction Diabetes and associated cardiovascular diseases (CVDs) are a class of disorders affecting the heart or blood vessels. Despite progress in clinical research and therapy, Abstract BS62 Figure 1 Abstracts A290 Heart 2023;109(Suppl 3):A1–A324 on October 16, 2023 by guest. Protected by copyright. http://heart.bmj.com/ Heart: first published as 10.1136/heartjnl-2023-BCS.275 on 2 June 2023. Downloaded from