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A Pathological Role for Protease‐Activated Receptor 2 in the Heart
Author(s) -
Pawlinski Rafal,
Antoniak Silvio,
Spring Denise,
Verrier Edward D.,
Blaxall Burns C.,
Mackman Nigel
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.110.7
Subject(s) - heart failure , medicine , inflammation , muscle hypertrophy , cardiology , receptor , pathological , endocrinology , ventricular remodeling , reperfusion injury , ischemia
We investigate the role of protease‐activated receptor 2 (PAR2) in heart pathology. PAR2 mRNA expression was analyzed by real‐time PCR in heart biopsies from patients with heart failure (HF). The role of PAR2 was investigated in mouse model of cardiac ischemia‐reperfusion (I/R) injury. Finally, we examined the effect of a cardiomyocyte‐specific overexpression of PAR2 in mice (TgPAR2). We found increased PAR2 mRNA levels in patients with ischemic HF (3.0±0.7fold) and idiopathic HF (4.3±0.6fold; P <.05 vs. controls). These levels returned to baseline after implantation of a LVAD. Interestingly, the infarct size was reduced in the hearts of PAR2−/− mice (24.3±1.7% vs. 35.8±3.4%; P <.05 vs. WT) after 2 h of reperfusion. This injury reduction was associated with less expression of pro‐inflammatory genes. PAR2−/− were protected from I/R injury‐induced heart remodeling determined by ECHO (PAR2−/− vs. WT: LV diameter: 1.43±0.06mm vs. 1.78±0.09mm; fractional shortening (FS): 49.3±1.2% vs. 40.9±1.6%; P <.05). Finally, we observed that 1 year old TgPAR2 mice developed heart hypertrophy with increased HW/BW ratio. ECHO analysis revealed that TgPAR2 mice had reduced heart function (FS: 38.3±5.1% vs. 24.5±6.7%; WT vs. TgPAR2; P <.05). These results indicate that PAR2 in the injured heart enhances inflammation and infarct size that leads to hypertrophy and HF. This study was supported by the AHA and NIH.