Fig. 8: PGAM5/MAVS signaling pathway is essential for the regulation of MARCH2 in I/R injury.

a Prior to I/R injury, WT mice were administrated with AAV9-cTnT-vector, AAV9-cTnT-MARCH2, AAV9-cTnT-PGAM5 or AAV9-cTnT-MAVS (2.0 × 10¹¹ V.g/mouse) for 3 weeks by tail vein injection. TTC/Evans Blue staining is used to depict infracted area. b Ratios of area at risk (AAR) to left ventricular (LV) area. c Infarct area normalized to AAR. No statistical significance for Vector-I/R vs MARCH2-PGAM5-I/R, no statistical significance for Vector-I/R vs MARCH2-MAVS-I/R. d, e Echocardiographic assessment of ejection fraction (EF, d) and fractional shortening (FS, e) in the indicated groups. No statistical significance for Vector-I/R vs MARCH2-PGAM5-I/R, no statistical significance for Vector-I/R vs MARCH2-MAVS-I/R. f, g LDH activity (f) and CK-MB level (g) in mouse with and without myocardial I/R. No statistical significance for Vector-I/R vs MARCH2-PGAM5-I/R; no statistical significance for Vector-I/R vs MARCH2-MAVS-I/R. h Representative western blotting results of MARCH2, PGAM5, mito-MAVS, caspase-1 (procaspase1; cleaved caspase-1), GSDMD (full-length; N-terminal), and IL-18 in hearts of the indicated group mice subjected to I/R (45 min/9 h). i IL-18 release was measured by ELISA in cardiac tissues of the indicated group mice subjected to I/R (45 min/9 h). No statistical significance for Vector-I/R vs MARCH2-PGAM5-I/R, no statistical significance for Vector-I/R vs MARCH2-MAVS-I/R. j A working model for MARCH2 function in I/R injury. MARCH2 interacts with and promotes the degradation of PGAM5 by facilitating its K48-linked polyUb, thus inhibiting the activity of MAVS/NLRP3 inflammasome pathway and cardiomyocyte pyroptosis. Data are shown as the means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001.