Royal College of Surgeons in Ireland
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The protein C pathways

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journal contribution
posted on 2024-01-08, 14:12 authored by Gemma LeonGemma Leon, Aisling M Rehill, Roger PrestonRoger Preston
Purpose of review: To provide an overview of the state-of-the-art in protein C (PC) pathway research.
Recent findings: The PC pathway is crucial for maintaining hemostasis to prevent venous thromboembolism. This is evident from genetic mutations that result in impaired PC pathway activity and contribute to increased venous thromboembolism risk in affected individuals. In addition to its anticoagulant role, activated PC (APC) also mediates a complex, pleiotropic role in the maintenance of vascular cell health, which it achieves via anti-inflammatory and antiapoptotic cell signaling on endothelial cells. Emerging data have demonstrated that cell signaling by APC, mediated by multiple receptor interactions on different cell types, also confers cytoprotective and anti-inflammatory benefits. Defects in both arms of the PC pathway are associated with increased susceptibility to thrombo-inflammatory disease in various preclinical thrombotic, proinflammatory and neurological disease models. Moreover, recent studies have identified attenuation of anticoagulant PC pathway activity as an exciting therapeutic opportunity to promote hemostasis in patients with inherited or acquired bleeding disorders.
Summary: In this review, we provide an overview of some recent developments in our understanding of the PC pathways.

Funding

Novel therapies for children with inflammatory bowel disease' | Funder: National Children’s Research Centre Crumlin / NCRC | Grant ID: C/18/3

Novel therapeutic approach to counter vaso-occlusive crisis in sickle cell disease using engineered activated protein C | Funder: National Children’s Research Centre Crumlin / NCRC | Grant ID: PRPG/H/18/315

New approaches to exploit coagulation protease-receptor signalling for therapeutic benefit | Funder: Science Foundation Ireland (SFI) | Grant ID: 21/FFP-A/8859

Science Foundation Ireland (15/CDA/3499, 20/COV/8511)

History

Comments

This is a pre-copyedited, author-produced version of an article accepted for publication in Current Opinion in Hematology. The published version of record Leon G, Rehill AM, Preston RJS. The protein C pathways. Curr Opin Hematol. 2022;29(5):251-258. is available online at: https://doi.org/10.1097/moh.0000000000000726

Published Citation

Leon G, Rehill AM, Preston RJS. The protein C pathways. Curr Opin Hematol. 2022;29(5):251-258.

Publication Date

1 September 2022

PubMed ID

35852855

Department/Unit

  • Irish Centre for Vascular Biology
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Health Professions Education
  • Immunity, Infection and Inflammation
  • Vascular Biology

Publisher

Lippincott Williams And Wilkins

Version

  • Accepted Version (Postprint)