Par-1–specific parmodulin ameliorates inflammasome activation in myocardial IRI. (A) Experimental design. (B-C) The biased PAR-1 antagonist parmodulin-2 (5 mg/kg) reduces the infarcted area to the same extent as aPC. Representative heart sections showing infarcted area detected by TTC staining (infarcted area encircled by dashed line; size bar, 20 µm) (B) and dot plot summarizing data (C). (D-H) Treatment of mice with parmodulin-2 reduces markers of inflammasome activation and mTORC1 signaling as efficiently as aPC. Representative immunoblots showing cardiac Nlrp3 expression and cl-Casp1 and cl–IL-1β (D) and bar graph summarizing results, with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as loading control (cont) (E). (D) Arrowheads indicate inactive (white) and active (black) forms of caspase-1 or IL-1β. (E) The active form was quantified. Dot plots summarizing plasma IL-1β (F) and representative immunoblots showing Raptor and HK1 expression and total and phosphorylated p70S6K (G) and bar graph summarizing results, with GAPDH as loading control (H). Sham-operated mice (sham) or mice with myocardial IRI without (cont; PBS) or with aPC (aPC) or parmodulin-2 (parmodulin) pretreatment. Data shown represent mean ± SEM of at least 6 mice per group (B-H). **P < .01; analysis of variance (C,E-F,H).