Coagulation protease-induced extracellular vesicles: their potential effects on coagulation and inflammation

Area of Science:

• Biochemistry
• Cell Biology
• Hematology

Background:

• Coagulation proteases activate protease-activated receptors (PARs), influencing cellular functions.
• PAR activation effects are cell-specific, but extracellular vesicles (EVs) mediate cross-talk between cell types.
• EVs are nanosized vesicles transferring bioactive molecules, enabling intercellular communication.

Purpose of the Study:

• To review how coagulation proteases, specifically factor VIIa (FVIIa), trigger EV release.
• To discuss the composition and function of FVIIa-released EVs.
• To explore the therapeutic potential of FVIIa-released EVs in bleeding and inflammatory conditions.

Main Methods:

• Review of existing literature on coagulation proteases, PARs, and EVs.
• Analysis of recent findings on FVIIa-induced EV release from vascular endothelium.
• Examination of EV cargo, including phosphatidylserine and microRNAs.

Main Results:

• FVIIa promotes EV release via endothelial cell protein C receptor-dependent PAR1 signaling.
• FVIIa-released EVs possess procoagulant and cytoprotective properties.
• These EVs are enriched with phosphatidylserine and anti-inflammatory microRNAs.

Conclusions:

• Coagulation proteases, particularly FVIIa, induce EV release that influences cellular responses and hemostasis.
• FVIIa-released EVs have therapeutic potential for treating bleeding and inflammatory disorders like hemophilic arthropathy.