Vidarabine, an anti-herpes agent, improves Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in mice

Figures

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  Fig. 1. Schematic illustration of experimental procedure and comparison of body weight, cardiac muscle weight, lung weight and liver weight. a Male 12-week-old C57BL/6 mice were divided into four groups: a normal control group (Control), a PG-LPS-treated group (L), a vidarabine-treated group (V), and a PG-LPS plus vidarabine-treated (L + V) group. Chronic infusion of vidarabine was performed for 1-week at a dose of 15 mg/kg/day with the osmotic mini-pumps and the indicated measurements were made. b The Control, PG-LPS, vidarabine and PG-LPS plus vidarabine groups showed similar body weight. NS, not significantly different from the Control (P > 0.05). One-way ANOVA followed by Tukey’s post hoc test). c No significant difference in heart (c), lung (d) or liver size in terms of weight per tibial length (TL) ratio (mg/mm) at 1 week after PG-LPS infusion among the four groups. P = NS, not significantly different from the Control. One-way ANOVA followed by the Tukey’s post hoc test). Data are presented as mean ± SD and scattered dots show individual data

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  Fig. 2. Effects of vidarabine on PG-LPS-induced fibrosis in the heart. a Representative images of Masson-trichrome-stained sections of cardiac muscle in the Control (upper left), PG-LPS (upper right), vidarabine (lower left), and BO + vidarabine (lower right) groups. Scale bar: 100 μm. b The area of fibrosis was significantly increased in the PG-LPS group (n = 7, **P < 0.01), but this increase was blocked in the PG-LPS + vidarabine group (n = 6, **P < 0.01). One-way ANOVA followed by Tukey’s post hoc test). c Expression of α-SMA, a fibrosis-related gene, was significantly increased in the cardiac muscle of PG-LPS group (n = 5, **P < 0.01), but this increase was blocked in the cardiac muscle of PG-LPS + vidarabine group (n = 5, *P < 0.05). One-way ANOVA followed by Tukey’s post hoc test). Full-size images of immunoblots are presented in Additional file 1: Fig. S1. Data are presented as mean ± SD and scattered dots show individual data

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  Fig. 3. Effects of vidarabine on PG-LPS-induced cardiac myocyte apoptosis. a Representative images of TUNEL-stained sections of cardiac muscle in the Control (upper left), PG-LPS (upper right), vidarabine (lower left), and PG-LPS + vidarabine (lower right) groups. Scale bar: 25 μm. b The number of TUNEL-positive myocyte was significantly increased in the PG-LPS group (n = 4, **P < 0.01), but this increase was blocked in the PG-LPS + vidarabine group (n = 5, **P < 0.01). One-way ANOVA followed by Tukey’s post hoc test). c Expression of anti-apoptotic BCL-2 protein was significantly decreased in the cardiac muscle of PG-LPS group (n = 7, **P < 0.01), but this change was significantly blocked in the cardiac muscle of PG-LPS + vidarabine group (n = 5, *P < 0.05). One-way ANOVA followed by Tukey’s post hoc test). Full-size images of immunoblots are presented in Additional file 1: Fig. S2. Data are presented as mean ± SD and scattered dots show individual data

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  Fig. 4. Effects of vidarabine on AC5, NOX4, p-CaMKII, ox-CaMKII and phospho-PLN. a AC5 expression was similar in cardiac muscle of all four groups. NS; not significantly different. One-way ANOVA followed. by Tukey’s post hoc test) Full-size images of immunoblots are presented in Additional file 1: Fig. S3. b NOX4 expression was significantly increased in the cardiac muscle of PG-LPS group (n = 7, *P < 0.05), and this increase was significantly blocked in the PG-LPS + vidarabine group (n = 7, *P < 0.05). One-way ANOVA followed by Tukey’s post hoc test). Full-size images of immunoblots are presented in Additional file 1: Fig. S4. c Expression of phospho-CaMKII (Thr-286) was significantly increased in the PG-LPS group (n = 6, **P < 0.01), and this increase was significantly attenuated in the PG-LPS + vidarabine group (n = 7, **P < 0.01). One-way ANOVA followed by Tukey’s post hoc test). Full-size images of immunoblots are presented in Additional file 1: Fig. S5. d Expression of oxidized-CaMKII (ox-CaMKII) was significantly increased in the PG-LPS group (n = 4, *P < 0.01) and this increase was significantly attenuated in the PG-LPS + vidarabine group (n = 4, *P < 0.05). One-way ANOVA…

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  Fig. 5. This scheme illustrates the proposed role of AC5 in the heart of PG-LPS-treated mice. Mice with experimental periodontitis induced by the ligation of the left first molar [39] or by chronic PG-LPS infusion as used in this study [18] show sympathetic overactivity. β-AR/GSα/AC5 signaling is activated by PG-LPS treatment, leading to ROS production via NOX4 and PLN phosphorylation at Thr-17. These changes might cause fibrosis and myocyte apoptosis in the heart of PG-LPS-treated mice, leading to cardiac dysfunction