Redox control of platelet functions in physiology and pathophysiology

An imbalance between the production and the detoxification of reactive oxygen species and reactive nitrogen species (ROS/RNS) can be implicated in many pathological processes. Platelets are best known as primary mediators of hemostasis and can be either targets of ROS/RNS or generate radicals during cell activation. These conditions can dramatically affect platelet physiology, leading even, as an ultimate event, to the cell number modification. In this case, pathological conditions such as thrombocytosis (promoted by increased cell number) or thrombocytopenia and myelodysplasia (promoted by cell decrease mediated by accelerated apoptosis) can occur.

Usually, in peripheral blood, ROS/RNS production is balanced by the rate of oxidant elimination. Under this condition, platelets are in a nonadherent "resting" state. During endothelial dysfunction or under pathological conditions, ROS/RNS production increases and the platelets respond with specific biochemical and morphologic changes. Mitochondria are at the center of these processes, being able to both generate ROS/RNS, that drive redox-sensitive events, and respond to ROS/RNS-mediated changes of the cellular redox state. Irregular function of platelets and enhanced interaction with leukocytes and endothelial cells can contribute to pathogenesis of atherosclerotic and thrombotic events.

The relationship between oxidative stress, platelet death, and the activation-dependent pathways that drive platelet pro-coagulant activity is unclear and deserves to be explored.

Expanding knowledge about how platelets can mediate hemostasis and modulate inflammation may lead to novel and effective therapeutic strategies for the long and growing list of pathological conditions that involve both thrombosis and inflammation.