Generation and characteristics of procoagulant platelets

Upon activation, a subpopulation of platelets adopts a necrotic procoagulant phenotype, which is characterized by bioenergetic failure of the cell. The molecular events underlying the formation of procoagulant platelets include calcium cytotoxicity and reactive oxygen species; both facilitate the cyclophilin D (CypD)-dependent formation of the mitochondrial permeability transition pore, leading to a decreased mitochondrial membrane potential and ATP depletion. Our research is focusing on better understand the formation of procoagulant platelets and their pathophysiological role in thrombosis and thrombo-inflammation. For this, we are currently analyzing the role of a mitochondrial enzyme in CypD-dependent procoagulant platelet formation and hypothesize that this enzyme protects platelet mitochondria from injury mechanisms that lead to platelet bioenergetic failure and necrosis. Next, we are studying procoagulant platelet formation in different thrombotic disorders using mouse models and patient samples. And last, we are investigating specific proinflammatory mediators secreted from procoagulant platelets, and their role in thrombo-inflammation. Altogether, this will increase our fundamental knowledge on platelet death, and may eventually reveal new therapeutic targets across a range of pathological conditions.