Fig. 4.

Cryopyrin- and P2X7 targeted interventions in acute myocardial infarction. (A) Cryopyrin- and P2X7 targeted small interfering (si)RNAs administered intraperitoneally 24 h before surgery leading to a >80% reduction in target protein expression (Western blot) and a significant reduction in caspase-1 activity. Treatment with a pharmacological P2X7 inhibitor (PPADS 25 mg/kg intraperitoneally daily) provided a similar effect on caspase-1 activity. Values are expressed as mean ± SEM % of control values; n = 4–6 per group, *P < 0.05 vs. sham-operated mice. (B and C) Histology (Masson's trichrome) of cardiac left ventricle midsections of mice 7 d after AMI and treatment with vehicle (NaCl 0.9%) or a P2X7 inhibitor (PPADS), respectively. (D–F) Reductions in ASC expression (Western blot, day 3) and in infarct size (Masson's trichrome, day 7) and apoptosis (in situ end labeling of DNA fragmentation, day 7), and in mice treated with a P2X7 inhibitor (PPADS) vs. vehicle (NaCl 0.9%) after AMI. Values are expressed as mean ± SEM; n = 4–6 per group, *P < 0.05 vs. sham-operated mice, ^†P < 0.05 vs. control AMI. (G and H) Monodimensional echocardiography recordings obtained 7 d after AMI in mice treated with NaCl 0.9% (control) or a P2X7 inhibitor (PPADS), respectively. (I–N) Reductions in left ventricular enlargement (end-diastolic and end-systolic diameters) in mice 7 d after AMI treated with a P2X7 inhibitor (PPADS) vs. vehicle, without any difference in left ventricular hypertrophy. (O–R) Similar reductions in left ventricular enlargement (end-diastolic and end-systolic diameters) in mice 7 d after AMI treated with silencing RNA targeted to cryopyrin and P2X7 but not with scrambled siRNA sequences. Values are expressed as mean ± SEM; n = 6–8 per group, *P < 0.05 vs. sham-operated mice, ^†P < 0.05 vs. control AMI.