Circadian nuclear receptor Rev-erbalpha is expressed by platelets and potentiates platelet activation and thrombus formation

Abstract Background Adverse cardiovascular events have day/night patterns with peaks in the morning, potentially related to endogenous circadian clock control of platelet activation. Circadian nuclear receptor Rev-erbα is an essential and negative component clock. Purpose We aim investigate expression profile biological function platelets. Methods results Here we report presence functions human mouse Both showed a rhythm that positively correlated aggregation. Global knockout platelet-specific mice exhibited defective hemostasis as assessed by prolonged tail-bleeding times. deletion also reduced ferric chloride-induced carotid arterial occlusive thrombosis, prevented collagen/epinephrine-induced pulmonary thromboembolism, protected against microvascular microthrombi obstruction infarct expansion acute myocardial infarction model. In vitro thrombus formation CD41-labeled fluorescence intensity was significantly blood. Platelets from impaired agonist-induced aggregation responses, integrin αIIbβ3 activation α-granule release. Consistently, pharmacological inhibition specific antagonists decreased markers both Mechanistically, mass spectrometry co-immunoprecipitation analyses revealed potentiated via oligophrenin-1-mediated RhoA/ERM (ezrin/radixin/moesin) pathway. Conclusion provide first evidence protein functionally expressed platelets potentiates formation. may serve novel therapeutic target for managing thrombosis-based disease. Funding Acknowledgement Type funding sources: Foundation. Main source(s): This work supported grants National Science Fund Distinguished Young Scholars (81625002), Natural Foundation China (81930007).