Abstract
Along with cancer, cardiovascular and cerebrovascular diseases remain by far the most common causes of death. Heart attacks and strokes are diseases in which platelets play a role, through activation on ruptured plaques and subsequent thrombus formation. Most platelet agonists activate platelets via G protein-coupled receptors (GPCRs), which make these receptors ideal targets for many antiplatelet drugs. However, little is known about the mechanisms that provide feedback regulation on GPCRs to limit platelet activation. Emerging evidence from our group and others strongly suggests that GPCR kinases (GRKs) are critical negative regulators during platelet activation and thrombus formation. In this review, we will summarize recent findings on the role of GRKs in platelet biology and how one specific GRK, GRK6, regulates the hemostatic response to vascular injury. Furthermore, we will discuss the potential role of GRKs in thrombotic disorders, such as thrombotic events in COVID-19 patients. Studies on the function of GRKs during platelet activation and thrombus formation have just recently begun, and a better understanding of the role of GRKs in hemostasis and thrombosis will provide a fruitful avenue for understanding the hemostatic response to injury. It may also lead to new therapeutic options for the treatment of thrombotic and cardiovascular disorders.
Highlights
Platelets are small, anucleate cells that circulate in the blood stream
In the past two decades, GPCR kinases (GRKs) have been shown to play an important role in the heart by regulating G protein-coupled receptors (GPCRs) signaling
GRKs have been extensively studied as therapeutic targets in cardiovascular disease
Summary
Anucleate cells that circulate in the blood stream. They originate from megakaryocytes, which are produced from the myeloid progenitor lineage of hematopoietic stem cells. Thrombin released as a consequence of the coagulation cascade accumulates at the site of vascular injury and cleaves protease-activated receptors (PARs) on the platelet surface (Figure 1A). Initiation of these signaling events at the site of. Signaling form isa driven rapid response mechanism that initiates recruitment of additional platelets into a growing thrombus requires mediators such as thrombin, platelet accumulation and thrombus growth at the site of injury.
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