Abstract
Ischemia–reperfusion (IR) injury is a common complication of a variety of cardiovascular
diseases, including ischemic stroke and myocardial infarction (MI). While timely re-establishment
of blood flow in a thrombosed artery is the primary goal of acute therapy in these
diseases, paradoxically, reperfusion of ischemic tissue can cause widespread microvascular
dysfunction that significantly exacerbates organ damage. Reperfusion injury is associated
with activation of the humoral and cellular components of the hemostatic and innate
immune systems and also with excessive reactive oxygen species production, endothelial
dysfunction, thrombosis, and inflammation. Platelets are critical mediators of thromboinflammation
during reperfusion injury and a hyperactive platelet phenotype may contribute to an
exaggerated IR injury response. This is particularly relevant to diabetes which is
characteristically associated with hyperactive platelets, significantly worse IR injury,
increased organ damage, and increased risk of death. However, the mechanisms underlying
vulnerability to IR injury in diabetic individuals is not well defined, nor the role
of “diabetic platelets” in this process. This review summarizes recent progress in
understanding the role of platelets in promoting microvascular dysfunction and inflammation
in the context of IR injury. Furthermore, the authors discuss aspects of the thromboinflammatory
function of platelets that are dysregulated in diabetes. They conclude that diabetes
likely enhances the capacity of platelets to mediate microvascular thrombosis and
inflammation during IR injury, which has potentially important implications for the
future design of antiplatelet agents that can reduce microvascular dysfunction and
inflammation.
Keywords
platelets - thromboinflammation - diabetes - ischemia–reperfusion injury
