Protease-activated receptors in endothelial health and dysfunction

Area of Science:

• Vascular Biology
• Cell Signaling
• Protease-Activated Receptors

Background:

• Protease-activated receptors (PARs) link extracellular proteases to intracellular signals in endothelial cells.
• PARs are critical regulators of coagulation, inflammation, and vascular stability.

Purpose of the Study:

• To review recent advancements in understanding endothelial PAR1-PAR4 signaling.
• To explore how protease specificity, receptor interactions, and signaling bias influence endothelial responses in health and disease.

Main Methods:

• Literature review of recent research on endothelial PAR signaling.
• Analysis of protease specificity, receptor interactions, and signaling bias.

Main Results:

• Endothelial PAR signaling is context-dependent.
• PAR1 exhibits biased signaling; thrombin disrupts barriers, while activated protein C (aPC) protects via β-arrestin.
• PAR2 regulates endothelial inflammation and vasodilation.
• PAR3 acts as a regulator, forming heterodimers with PAR1.
• PAR4 activation leads to barrier dysfunction and thromboinflammation.

Conclusions:

• Endothelial PARs are sophisticated sensors of the vascular protease environment.
• Future therapies will focus on pathway-specific modulation rather than broad blocking.
• New avenues for precise vascular treatments are emerging.