Synergistic activation of PAR1 and inhibition of PAR2 activity abolish cardioprotection in TFΔCT mice. (A) Experimental outline. TFΔCT mice, immediately prior to MI, were implanted with osmotic minipump supplemented with either the cocktail of PAR1 agonist and PAR2 antagonist peptides or the control peptide. Cardiac function was monitored by echocardiography. (B) The Kaplan-Meier survival curves. Log-rank test; n = 6 for TFΔCT mice infused with the control peptide, and n = 7 for TFΔCT mice infused with the cocktail of PAR1 agonist and PAR2 antagonist peptides, and n = 9 for WT mice serving as a control group. (C, D) LVEF and LVIDs determined by echocardiography for survived mice. **P < 0.01, ***p < 0.001 compared with TFΔCT mice infused with the control peptide by two-way ANOVA with Bonferroni post hoc test; n = 5 for both control peptide group and treatment group of TFΔCT mice, and n = 6 for WT mice. Of note, in panel D, the difference between WT mice and TFΔCT mice infused with the cocktail of PAR1 agonist and PAR2 antagonist peptides is not significant, but the difference between WT mice and TFΔCT mice infused with the control peptide was highly significant (p < 0.01).