Protease-activated receptor-2 activation improves efficiency of experimental ischemic preconditioning.
Protease-activated receptor-2 (PAR-2) is a member of seven transmembrane domain G protein-coupled receptors activated by proteolytic cleavage. PAR-2 is involved in inflammatory events and cardiac ischemic reperfusion injury. The objective of this study was to investigate the effects of PAR-2 in experimental myocardial ischemic preconditioning. To monitor the effects of PAR-2, Langendorff-perfused rat hearts were used. These hearts were treated with PAR-2-activating peptide (PAR-2AP) in various protocols. Hemodynamic parameters (left ventricular developed pressure, left ventricular diastolic pressure, coronary flow rate, and heart rate), several indexes of oxidative injury, and neutrophil accumulation were evaluated. We show for the first time that enhanced PAR-2 activation improves efficiency of ischemic preconditioning and reduces cardiac inflammation in the rat heart. Indeed, after PAR-2AP infusion we found that hemodynamic parameters, oxidative injury, infarct size, and neutrophil accumulation were involved. These data support the concept that PAR-2-dependent cell trafficking may regulate signaling responses to cardiac ischemia and inflammation.
Napoli
Claudio
C
Department of Medicine, Federico II University of Naples, Italy.
De Nigris
Filomena
F
Cicala
Carla
C
Wallace
John L
JL
Caliendo
Giuseppe
G
Condorelli
Mario
M
Santagada
Vincenzo
V
Cirino
Giuseppe
G
D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000378:metabolism; D003971:Diastole; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D006339:Heart Rate; D006439:Hemodynamics; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D016277:Ventricular Function, Left
D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D005978:Glutathione