Fig. 2: Cardiomyocyte-specific conditional knockout of MacroD1 protects the heart against injury and dysfunction induced by LPS or cecal ligation and puncture (CLP) surgery in mice. | Nature Communications

Fig. 2: Cardiomyocyte-specific conditional knockout of MacroD1 protects the heart against injury and dysfunction induced by LPS or cecal ligation and puncture (CLP) surgery in mice.

From: Cardiomyocyte mitochondrial mono-ADP-ribosylation dictates cardiac tolerance to sepsis by configuring bioenergetic reserve in male mice

Fig. 2

A Schematic overview of the breeding strategy for creating mice with an inducible, heart-specific MacroD1 knockout. Mice carrying the αMHC-MCM+ MacroD1flox/flox genotype, and upon tamoxifen induction, served as the experimental group (cKO). MacroD1flox/flox littermate mice (Flox) constituted the control cohort. B Western blotting validation of the knockout of MacroD1 in left ventricular tissues and quadriceps muscle from 10-week-old mice. C Kaplan-Meier survival rates analysis of 10-week-old mice subjected to intraperitoneal injection of LPS (10 mg/kg) within 96 h (n = 15). D–F Representative echocardiography (D) and echocardiographic analysis (E, F) in mice 18 h after LPS or saline administration (LVEF: left ventricular ejection fraction; LVFS: left ventricular fractional shortening; n = 7 mice for Flox and cKO; n = 8 mice for Flox + LPS and cKO + LPS). G and H, Serum levels of lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) in Flox and cKO mice injected intraperitoneally with/without LPS for 18 h (n = 5 mice for Flox and cKO; n = 7 mice for Flox + LPS and cKO + LPS). I–K Immunofluorescent staining and quantitative analysis of Myeloperoxidase (MPO; I and J) and α-smooth muscle actin (α-SMA; I and J), and MASSON staining and quantification (I, K) in heart sections. MPO staining was performed from mice 18 h after LPS injection, and α-SMA and MASSON stainings were performed from mice 96 hours after LPS injection (n = 5 for J; n = 6 for K). L Kaplan-Meier survival rates analysis of mice subjected to CLP surgery within 96 hours (n = 15). M–O Representative echocardiography (M) and echocardiographic analysis (N, O) in mice 24 h after CLP or sham surgery (n = 6). P, Q Serum levels of LDH and cTnT in mice 24 h after CLP surgery (n = 5). R, S MPO and α-SMA immunofluorescent staining and quantitative analysis of heart tissues. MPO and α-SMA staining was performed on mice 24 h and 96 h after CLP or sham surgery, respectively (n = 5). Data are shown as the mean ± SD. Data analysis was conducted utilizing one-way ANOVA with Tukey’s multiple comparison test. The log-rank test was employed to analyze survival data. Source data are provided as a Source Data file.

Back to article page