Thrombosis in diabetes: a shear flow effect?

Abstract

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.