UCP2 inhibition exaggerates diabetic cardiomyopathy by facilitating the activation of NLRP3 and pyroptosis

Figures

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  Fig. 1. Experimental design. (A) A schematic diagram of experimental design. (B, C) Expression of UCP2 protein in heart tissues in all groups (n = 10 mice per group). β-actin was used as an internal reference. *P < 0.05, **P < 0.01, and ***P < 0.001 vs. Ctrl group

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  Fig. 2. UCP2 inhibition aggravates cardiac dysfunction and myocardial injury in DCM mice. All data presented were obtained from n = 10 mice per group. (A) Representative echocardiographic images of mice in various groups. (B, C) Ejection fraction (EF) and fractional shortening (FS) in each group. (D, E) The results of LVPW thickness and E/A ratio of mice in each group. (F, I) Representative images of Masson staining and statistics of myocardial fibrosis area in heart tissues of each group. (G, J) Representative images of WGA staining and statistics of cross-sectional area in heart tissues of each group. (H, K) Representative images of immunohistochemical staining and statistics of F4/80 positive area in heart tissues of each group. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 vs. Ctrl group; #P < 0.05, ##P < 0.01 vs. DCM group

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  Fig. 3. UCP2 deficiency facilitates NLRP3 activation and pyroptosis in DCM mice. All data presented were obtained from n = 10 mice per group. (A, B) Immunofluorescent staining of NLRP3 and quantitative analysis. (C) Expression of TXNIP, NLRP3, GSDMD and IL-1β and IL-18. (D-H) Quantitative analysis of C.*P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 vs. Ctrl group; ##P < 0.01 vs. DCM group

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  Fig. 4. UCP2 knockdown deteriorates cell injury and mitochondrial dysfunction in high glucose and sodium palmitate-induced H9C2 cells. (A, B) UCP2 protein expressions and quantitative analysis in each group. (C) Cell viability of each group. (D) LDH release in each group. (E, G) Representative images and and quantitative analysis of DCFH-DA fluorescence for cells in each group. (F, H) Representative staining images of JC-1 and quantified analysis for cells in each group. (I) Expression of TXNIP and NLRP3 for cells in each group. (J, K) Quantitative analysis of I. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 vs. Ctrl group; #P < 0.05, ##P < 0.01, and ###P < 0.001 vs. HG group

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  Fig. 5. UCP2 knockdown promotes pyroptosis in high glucose and sodium palmitate-stimulated H9C2 cell. (A) Representative immunofluorescent staining images and partial enlargement of images of cellular GSDMD signal in each group. The yellow arrow represents cellular membrane pores. (B) The cellular expression of GSDMD and its downstream molecules in each group. (C-E) Quantitative analysis of B. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 vs. Ctrl group; ###P < 0.001 vs. HG group