Cardioprotective Effect of Decorin in Type 2 Diabetes

Figures

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  Figure 1. The recombinant adeno-associated viral vector mediated decorin (DCN) expression in heart tissue both in protein and mRNA level. (A, B) Western blot analysis showed that the expression levels of DCN protein was upregulated in the group received rAAV-DCN. (C) Real-time RT-PCR showed that DCN mRNA was significantly increased after rAAV-DCN administration. Values are means ± SD. *P < 0.05, **P < 0.01.

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  Figure 2. Effect of rAAV-decorin (DCN) treatment on glucose metabolism. (A) Fasting blood glucose were measured every two weeks throughout the study. (B) Plasma glucose levels during oral glucose tolerance tests (OGTT) after 6 months treatment. Values are means ± SD. *P < 0.05 diabetes mellitus (DM) group vs. control group.

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  Figure 3. Overexpression of decorin (DCN) improved cardiac dysfunction in the diabetic rats. (A) The Dp/Dt maximum level (Dp/Dt max) evaluated by cardiac catheter; (B) The Dp/Dt minimum level (Dp/Dt min) evaluated by cardiac catheter; (C) End-diastolic pressure of left ventricular (LVEDP) evaluated by cardiac catheter; (D) Ejection fraction (EF) evaluated by echocardiography; (E) Fractional shortening (FS) evaluated by echocardiography; (F) left ventricular internal dimension (LVID) evaluated by echocardiography. Values are means ± SD. *P < 0.05, **P < 0.01 vs. control; #P < 0.05, ##P < 0.01 vs. DM+control.

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  Figure 4. Decorin (DCN) overexpression attenuated myocardial fibrosis in diabetic rats. (A) Collagen deposition in cardiac tissues indicated by Sirius red staining. (B) The ratio of the fibrosis area evaluated with image pro plus software; (C) The mRNA levels of collagen type 1 (Col 1A1, Col 1A2) and type 3 (Col 3A1) assessed by real-time RT-PCR. GAPDH was served as housekeeping gene. Values are means ± SD. *P < 0.05, **P < 0.01 vs. control; #P < 0.05, ##P < 0.01 vs. DM+control.

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  Figure 5. TGFβ pathway was involved in the protection of decorin (DCN) against myocardial fibrosis in diabetes. (A–C) The protein level of TGFβ1 (A, B) and α-SMA (A, C) detected by western blot; (D) The mRNA expression of TGFβ1 in heart tissue; (E) The concentration of TGFβ1 in plasma; (F–H) the phosphorylation level of ERK1/2 (F, G) and smad2 (F, H). Values are means ± SD. *P < 0.05, **P < 0.01 vs. control vs. control; #P < 0.05, ##P < 0.01 vs. DM+control.

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  Figure 6. Overexpression of decorin (DCN) reduced inflammation in the diabetic animals. (A) HE staining of heart sections; (B–E) mRNA level of IL-1α (B), IL-1β (C), MCP-1 (D), and IL-6 (E) were determined by real-time RT-PCR, respectively; (F–I) Concentration of plasma IL-1α (F), IL-1β (G), MCP-1 (H), and IL-6 (I) were determined by ELISA, respectively. Values are means ± SD. *P < 0.05, **P < 0.01 vs. control vs. control; #P < 0.05, ##P < 0.01 vs. DM+control.

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  Figure 7. NF-κB and IGF-IR/PKCα/hsp70 pathway were involved in the protection of decorin (DCN) against diabetic cardiomyopathy (DCM). (A–C) The expression of p-IκB, T-IκB, cytoplasmic P65, and nuclear P65. β-actin were used for cytoplasmic control and lamin B were used for nuclear control. (D–H) the expression of IGFIR (D, E), p-PKCα (D, F), T-PKCα (D, G) as well as HSP70 (D, H) were determined by Western blots. Values are means ± SD. *P < 0.05, **P < 0.01 vs. control; #P < 0.05, ##P < 0.01 vs. DM+control.