PAR2 Regulates Cardiac Pressure and Vascular Function Through Context-Dependent Signalling Mechanisms

Area of Science:

• Cardiovascular Physiology
• G protein-coupled receptor signaling
• Vascular Biology

Background:

• Proteinase-activated receptor-2 (PAR2) influences cardiovascular regulation via G protein-coupled receptor signaling.
• Understanding PAR2's role in cardiac pressure and vascular function is crucial for cardiovascular health.

Purpose of the Study:

• To investigate the baseline cardiovascular phenotype of PAR2-deficient (PAR2-/-) mice.
• To determine the in vivo effects of the PAR2 agonist tcLIGRLO on cardiovascular function.

Main Methods:

• Left ventricular pressure-volume (PV) analysis in PAR2-/- mice.
• In vivo administration of the PAR2 agonist tcLIGRLO in wild-type (WT) and PAR2-/- mice.
• Ex vivo assessment of vascular responses in PAR2-/- arteries.

Main Results:

• PAR2-/- mice exhibited elevated systolic and diastolic pressures, increased ejection fraction, and preserved global cardiac function.
• tcLIGRLO reduced cardiac pressure, contractility, and stroke work in WT mice, but not in PAR2-/- mice, indicating PAR2-dependent cardiac regulation.
• tcLIGRLO induced strain-dependent vascular responses in PAR2-/- mice, involving Gq-dependent signaling in arteries.

Conclusions:

• PAR2 acts as a context-dependent regulator of cardiac pressure and vascular tone.
• PAR2-dependent cardiac effects and PAR2-independent vascular responses involve distinct signaling pathways.
• These findings highlight the complex role of PAR2 in cardiovascular homeostasis.