BACKGROUND: Patency rates after coronary artery bypass grafting (CABG) are better if the internal mammary artery (IMA) is used rather than the greater saphenous vein (GSV), and may be related to the endothelial release of vasodilators antagonizing vascular contraction. It has recently been shown that a family of protease-activated receptors (PARs) modulate endothelium-dependent vasodilatation. OBJECTIVE AND METHODS: The aim of this study was to evaluate the presence and functional role of protease-activated receptor 1 (PAR1) and protease-activated receptor 2 (PAR2) in mediating vascular tone in IMAs and GSVs from patients undergoing CABG by means of real time-PCR and isometric tension measurements. RESULTS: PAR1 mRNA levels were higher than those of PAR2 mRNA in both vessels. A selective PAR2-activating peptide (PAR2-AP), SLIGKV-NH(2) (0.01-100 micromol L(-1)), failed to induce vasorelaxation in precontracted IMA and GSV rings, whereas the selective PAR1-AP, TFLLR-NH(2) (0.001 to 10 micromol L(-1)), caused greater endothelium-dependent relaxation in the IMAs (pD(2) values 7.25 +/- 0.6 vs. 7.86 +/- 0.42, P < 0.05; E(max) values 56.2 +/- 17.3% vs. 29.7 +/- 13.4%, P < 0.001). Preincubation with TNFalpha (3 nmol L(-1)) induced vasorelaxation in IMAs in response to PAR2-AP (P < 0.05 vs. non-stimulated vessels); the response to PAR1-AP was unchanged. The relaxation induced by both PAR-APs was NO- and endothelium-dependent. CONCLUSION: These data show that functionally active PAR1 and PAR2 are present in IMAs and GSVs, and that inflammatory stimuli selectively enhance endothelium-dependent relaxation to PAR2-AP in IMAs.
Distinct roles for PAR1- and PAR2-mediated vasomotor modulation in human arterial and venous conduits / R. Ballerio, M. Brambilla, D. Colnago, A. Parolari, M. Agrifoglio, M. Camera, E. Tremoli, L. Mussoni. - In: JOURNAL OF THROMBOSIS AND HAEMOSTASIS. - ISSN 1538-7933. - 5:1(2007), pp. 174-180.
|Titolo:||Distinct roles for PAR1- and PAR2-mediated vasomotor modulation in human arterial and venous conduits|
BRAMBILLA, MARTA (Secondo)
TREMOLI, ELENA (Penultimo)
MUSSONI, LUCIANA (Ultimo)
|Parole Chiave:||Coronary artery bypass; Grafting isometric tension; Mammary artery; Protease-activated receptors; Saphenous vein; TNF-alpha|
|Settore Scientifico Disciplinare:||Settore MED/23 - Chirurgia Cardiaca|
Settore BIO/14 - Farmacologia
|Data di pubblicazione:||2007|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1538-7836.2006.02265.x|
|Appare nelle tipologie:||01 - Articolo su periodico|