Protease-activated receptor 2 deficiency reduces cardiac ischemia/reperfusion injury.
OBJECTIVE
To investigate the effect of protease-activated receptor (PAR) 2 deficiency on ischemia/reperfusion (I/R) injury-induced infarct size, inflammation, heart remodeling, and cardiac function.


RESULTS
PAR-2 signaling enhances inflammation in different diseases. The effect of PAR-2 deficiency in cardiac I/R injury is unknown. PAR-2(-/-) mice and wild-type littermates were subjected to 30 minutes of ischemia and up to 4 weeks of reperfusion. Infarct size, oxidative/nitrative stress, phosphorylation of mitogen-activated protein kinases, and inflammatory gene expression were assessed 2 hours after reperfusion. Changes in heart size and function were measured by echocardiography up to 4 weeks after reperfusion. Infarct size was significantly reduced in hearts of PAR-2(-/-) mice compared with wild-type littermates. In addition, oxidative/nitrative stress, phosphorylation of mitogen-activated protein kinase, and expression of proinflammatory genes were significantly attenuated in injured hearts of PAR-2(-/-) mice. Finally, PAR-2(-/-) mice were protected from postinfarction remodeling and showed less impairment in heart function compared with wild-type littermates up to 4 weeks after I/R injury.


CONCLUSIONS
PAR-2 deficiency reduces myocardial infarction and heart remodeling after I/R injury.
Antoniak
Silvio
S
Division of Hematology/Oncology, Department of Medicine, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7035, USA.
Rojas
Mauricio
M
Spring
Denise
D
Bullard
Tara A
TA
Verrier
Edward D
ED
Blaxall
Burns C
BC
Mackman
Nigel
N
Pawlinski
Rafal
R
D000328:Adult; D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure; D006801:Humans; D007249:Inflammation; D008297:Male; D051379:Mice; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D044464:Receptor, PAR-2 / Q000172:deficiency*; D020257:Ventricular Remodeling
D044464:Receptor, PAR-2