Distinct roles for PAR1- and PAR2-mediated vasomotor modulation in human arterial and venous conduits

Area of Science:

• Vascular biology
• Cardiovascular surgery
• Molecular pharmacology

Background:

• Coronary artery bypass grafting (CABG) patency is superior with the internal mammary artery (IMA) compared to the greater saphenous vein (GSV).
• Endothelial release of vasodilators is implicated in IMA's superior patency, potentially involving protease-activated receptors (PARs).

Purpose of the Study:

• To investigate the presence and functional role of protease-activated receptor 1 (PAR1) and protease-activated receptor 2 (PAR2) in IMA and GSV vascular tone.
• To assess the impact of PAR1 and PAR2 activation on vasoreactivity in vessels used for CABG.

Main Methods:

• Real-time PCR was used to quantify PAR1 and PAR2 mRNA expression in IMA and GSV.
• Isometric tension measurements were performed on precontracted IMA and GSV rings to assess responses to selective PAR1-activating peptide (TFLLR-NH(2)) and PAR2-activating peptide (SLIGKV-NH(2)).
• The effect of tumor necrosis factor-alpha (TNFα) on PAR-mediated responses was evaluated.

Main Results:

• PAR1 mRNA expression was significantly higher than PAR2 mRNA in both IMA and GSV.
• Selective PAR1-activating peptide induced greater endothelium-dependent relaxation in IMAs compared to GSVs.
• A selective PAR2-activating peptide did not induce vasorelaxation in either vessel unless pre-incubated with TNFα, which enhanced PAR2-mediated relaxation specifically in IMAs.
• Both PAR1- and PAR2-mediated relaxations were nitric oxide (NO)- and endothelium-dependent.

Conclusions:

• Functionally active PAR1 and PAR2 are present in both IMAs and GSVs.
• PAR1 plays a significant role in mediating endothelium-dependent relaxation in both arterial grafts.
• Inflammatory stimuli can selectively enhance endothelium-dependent relaxation mediated by PAR2 in IMAs, suggesting a role in graft adaptation or dysfunction.