Post-transcriptional control of hemostatic genes: mechanisms and emerging therapeutic concepts in thrombo-inflammatory disorders.

The hemostatic system is pivotal to maintaining vascular integrity. Multiple components involved in blood coagulation have central functions in inflammation and immunity. A derailed hemostasis is common in prevalent pathologies such as sepsis, cardiovascular disorders and, lately, COVID-19. Physiological mechanisms limit the deleterious consequences of a hyperactivated hemostatic system through adaptive changes in gene expression. While this is mainly regulated at the level of transcription, co- and posttranscriptional mechanisms are increasingly perceived as central hubs governing multiple facets of the hemostatic system. This layer of regulation modulates the biogenesis of hemostatic components, for example in situations of increased turnover and demand. However, they can also be 'hijacked' in disease processes, thereby perpetuating and even causally entertaining associated pathologies. This review summarizes examples and emerging concepts that illustrate the importance of posttranscriptional mechanisms in hemostatic control and crosstalk with the immune system. It also discusses how such regulatory principles can be used to usher in new therapeutic concepts to combat global medical threats such as sepsis or cardiovascular disorders.