Long-term serotonin reuptake inhibition depleted platelet serotonin, reducing neutrophil degranulation and preserving cardiac function in mice, and lowering CD11b and myeloperoxidase in humans.
Does depletion of platelet serotonin reduce thromboinflammation and myocardial ischemia/reperfusion injury in mouse models and patients?
Platelet serotonin aggravates myocardial ischemia/reperfusion injury by promoting neutrophil degranulation, suggesting serotonin depletion may offer a therapeutic target for thromboinflammation.
BACKGROUND: Platelets store large amounts of serotonin that they release during thrombus formation or acute inflammation. This facilitates hemostasis and modulates the inflammatory response. METHODS: Infarct size, heart function, and inflammatory cell composition were analyzed in mouse models of myocardial reperfusion injury with genetic and pharmacological depletion of platelet serotonin. These studies were complemented by in vitro serotonin stimulation assays of platelets and leukocytes in mice and men, and by measuring plasma serotonin levels and leukocyte activation in patients with acute coronary syndrome. RESULTS: ) and increased expression of membrane-bound leukocyte adhesion molecule CD11b, leading to enhanced inflammation in the infarct area and reduced myocardial salvage. In patients hospitalized with acute coronary syndrome, plasmatic serotonin levels correlated with CD11b expression on neutrophils and myeloperoxidase plasma levels. Long-term serotonin reuptake inhibition-reported to protect patients with depression from cardiovascular events-resulted in the depletion of platelet serotonin stores in mice. These mice displayed a reduction in neutrophil degranulation and preserved cardiac function. In line, patients with depression using serotonin reuptake inhibition, presented with suppressed levels of CD11b surface expression on neutrophils and lower myeloperoxidase levels in blood. CONCLUSIONS: Taken together, we identify serotonin as a potent therapeutic target in neutrophil-dependent thromboinflammation during myocardial reperfusion injury.
Mauler et al. (Thu,) conducted a other in Myocardial ischemia/reperfusion injury and acute coronary syndrome. Serotonin reuptake inhibition was evaluated on Neutrophil degranulation, cardiac function, CD11b expression, and myeloperoxidase levels. Long-term serotonin reuptake inhibition depleted platelet serotonin, reducing neutrophil degranulation and preserving cardiac function in mice, and lowering CD11b and myeloperoxidase in humans.