Endothelial PAR2 activation evokes resistance artery relaxation

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Signaling
• G Protein-Coupled Receptors

Background:

• Protease-activated receptors (PAR1 and PAR2) are present in cardiovascular tissues.
• PARs may influence blood pressure through vascular contraction/relaxation via endothelial calcium (Ca2+) signaling.
• Mechanisms of PAR-mediated vascular regulation are not fully understood.

Purpose of the Study:

• To investigate PAR1 and PAR2 regulation of blood vessel function.
• To explore PAR-mediated endothelial Ca2+ signaling pathways.
• To elucidate the role of PARs in vascular contraction and relaxation.

Main Methods:

• Single-cell Ca2+ imaging in intact blood vessels.
• Utilized PAR1 and PAR2 specific activators.
• Measured mesenteric artery responses to receptor activation.

Main Results:

• PAR2 activation induced multicellular Ca2+ waves in endothelial cells, distinct from muscarinic receptor activation.
• PAR2 activated specific endothelial cell clusters, segregating signal processing.
• PAR2 is a phospholipase C-coupled receptor, releasing Ca2+ from IP3-sensitive stores, leading to endothelium-dependent relaxation.
• PAR1 activation did not affect endothelial Ca2+ signaling or mesenteric artery tone.

Conclusions:

• Endothelial PAR2, not PAR1, mediates mesenteric artery relaxation.
• PAR2 signaling involves IP3-mediated Ca2+ release from internal stores.
• PAR2-mediated sensing is spatially segregated to distinct endothelial cell clusters.