Cardiovascular events are the major cause of morbidity and mortality in Type 2 diabetes (T2D). This condition is associated with heightened platelet reactivity, contributing to increased atherothrombotic risk. Indeed, individuals with diabetes respond inadequately to standard antiplatelet therapy. Furthermore, they often experience recurrent events as well as side effects that include excess bleeding. This highlights the need for identification of novel regulators of diabetes-associated thrombosis to target for therapeutic intervention. It is well established that platelet aggregation, a process essential for thrombus formation, is tightly regulated by shear stress; however, the mechanisms underlying shear activation of platelets, particularly in the setting of diabetes, are still poorly understood. This review will address the limitations of current diagnostic systems to assess the importance of shear stress in the regulation of thrombus formation in T2D, and the inability to recapitulate the pro-thrombotic phenotype seen clinically in the setting of T2D. Moreover, we will discuss recent findings utilizing new technologies to define the importance of shear stress in thrombus formation and their potential application to the setting of diabetes. Finally, we will discuss the potential of targeting shear-dependent mechanisms of thrombus formation as a novel therapeutic approach in the setting of T2D.
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June 2017
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The accompanying caption is: Image demonstrates a 3D reconstruction of the neurovascular unit in a hippocampal artery in the mouse brain. For further details, see article by Nizari et al in this issue, pages 1207-1214. Image kindly provided by Cheryl Hawkes.
Review Article|
June 07 2017
Thrombosis in diabetes: a shear flow effect?
Erik Westein;
1Vascular Biomechanics Group, Baker Heart and Diabetes Institute, Melbourne, Australia
3Central Clinical School, Monash University, Melbourne, Australia
Correspondence: Erik Westein ([email protected])
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Thomas Hoefer;
Thomas Hoefer
1Vascular Biomechanics Group, Baker Heart and Diabetes Institute, Melbourne, Australia
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Anna C. Calkin
Anna C. Calkin
2Lipid Metabolism and Cardiometabolic Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
3Central Clinical School, Monash University, Melbourne, Australia
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Publisher: Portland Press Ltd
Received:
October 03 2016
Revision Received:
February 14 2017
Accepted:
February 27 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (12): 1245–1260.
Article history
Received:
October 03 2016
Revision Received:
February 14 2017
Accepted:
February 27 2017
Citation
Erik Westein, Thomas Hoefer, Anna C. Calkin; Thrombosis in diabetes: a shear flow effect?. Clin Sci (Lond) 1 June 2017; 131 (12): 1245–1260. doi: https://doi.org/10.1042/CS20160391
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