Page 32 - Haematologica Vol. 109 - July 2024

SPOTLIGHT REVIEW ARTICLE - Coagulation factors and endothelial functionality C. Olgasi et al.
Figure 1. Coagulation factors binding to receptors involved in endothelial cell functions. Antithrombin binds to heparan sulfate proteoglycans (HSPG) to exert its function in endothelial cells (EC). Thrombomodulin can induce the expression of genes involved in extracellular matrix and angiogenesis. Thrombin and tissue factor bind G-protein coupled receptors and integrins. von Wille- brand factor (vWF) binds integrin on EC and activated protein C (APC) binds G-protein coupled receptors and receptor tyrosine kinases (RTK). Factor VIII (FVIII) binds to known scavenger receptors, but its involvement with integrins or RTK in the regulation of EC functionality has never been fully explored. The activation of these receptors induces the expression of genes involved in extracellular matrix organization and angiogenesis modulating EC functions.
for conditions where both coagulation and angiogenesis are impaired, such as vascular diseases and cancer. For example, FVIII is expressed by several tumors independently of vWF expression, suggesting a possible unique role of FVIII in cancer physiopathology.54
Revealing the multifaceted roles of CF uncovers novel physiological mechanisms, shedding light on their func- tions beyond conventional hemostasis. While selected CF have already been the subject of initial studies, others await deeper exploration, suggesting an exciting trajectory in understanding their involvement in endothelial biology.
Disclosures
No conflicts of interest to disclose.
Contributions
CO, SA, AC and AF wrote and revised the manuscript. CO generated the figure using BioRender tool (Agreement N: HV26FVNYFH). AF conceived, wrote, and revised the man- uscript.
Acknowledgments
The authors thank Dr. Chiara Borsotti and Saicharan Akula for their help in critically reading and revising the manu- script.
Funding
This work was partially supported by a Telethon grant (N. GGP19201 to AF) and Bando per la Ricerca Roche to CO.
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