Cardeza Foundation for Hematologic Research, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cyrus Tang Hematology Center, Soochow University, Suzhou 215123, China.
Int J Mol Sci. 2020 Jul 28;21(15):5345. doi: 10.3390/ijms21155345.
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.
除癌症外，心血管和脑血管疾病仍是目前最常见的死亡原因。心脏病发作和中风是血小板起作用的疾病，通过破裂斑块上的血小板激活和随后的血栓形成。大多数血小板激动剂通过 G 蛋白偶联受体 (GPCR) 激活血小板，这使得这些受体成为许多抗血小板药物的理想靶点。然而，对于提供反馈调节 GPCR 以限制血小板激活的机制知之甚少。我们小组和其他小组的新证据强烈表明，GPCR 激酶 (GRK) 在血小板激活和血栓形成过程中是关键的负调控因子。在这篇综述中，我们将总结 GRK 在血小板生物学中的作用的最新发现，以及特定的 GRK6 如何调节血管损伤的止血反应。此外，我们将讨论 GRK 在血栓性疾病中的潜在作用，例如 COVID-19 患者的血栓事件。关于 GRK 在血小板激活和血栓形成过程中的功能的研究刚刚开始，更好地了解 GRK 在止血和血栓形成中的作用将为理解损伤后的止血反应提供一条富有成效的途径。它也可能为治疗血栓形成和心血管疾病提供新的治疗选择。
