Journal article

Apoptotic Ablation of Platelets Reduces Atherosclerosis in Mice With Diabetes

Man KS Lee, Michael J Kraakman, Dragana Dragoljevic, Nordin MJ Hanssen, Michelle C Flynn, Annas Al-Sharea, Gopalkrishna Sreejit, Camilla Bertuzzo-Veiga, Olivia D Cooney, Fatima Baig, Elizabeth Morriss, Mark E Cooper, Emma C Josefsson, Benjamin T Kile, Prabhakara R Nagareddy, Andrew J Murphy



OBJECTIVE: People with diabetes are at a significantly higher risk of cardiovascular disease, in part, due to accelerated atherosclerosis. Diabetic subjects have increased number of platelets that are activated, more reactive, and respond suboptimally to antiplatelet therapies. We hypothesized that reducing platelet numbers by inducing their premature apoptotic death would decrease atherosclerosis. Approach and Results: This was achieved by targeting the antiapoptotic protein Bcl-xL (B-cell lymphoma-extra large; which is essential for platelet viability) via distinct genetic and pharmacological approaches. In the former, we transplanted bone marrow from mice carrying the Tyr15 to Cys loss of..

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University of Melbourne Researchers


Awarded by National Health and Medical Research Council (NHMRC)

Awarded by Murphy and National Institutes of Health

Awarded by Dutch Heart Foundation

Awarded by Dutch Diabetes Foundation

Awarded by NHMRC

Awarded by National Heart Foundation

Funding Acknowledgements

This work was supported by National Health and Medical Research Council (NHMRC) grant (APP1106154) to A.J. Murphy and National Institutes of Health (R01HL137799 and R00HL122505) to P.R. Nagareddy. N.M.J. Hanssen is supported by the Dutch Heart Foundation (2017T039), Dutch Diabetes Foundation (2017.85.005), and the European Foundation for the Study of Diabetes. A.J. Murphy is supported by Career Development Fellowship from the NHMRC (APP1085752), a Future Leader Fellowship from the National Heart Foundation (100440), a Viertel Award from Diabetes Australia Research Trust and a Centenary Award from CSL. E.C. Josefsson is the recipient of a fellowship from the Lorenzo and Pamela Galli Charitable Trust.