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I(f) current channel inhibitor (ivabradine) deserves cardioprotective effect via down-regulating the expression of matrix metalloproteinase (MMP)-2 and attenuating apoptosis in diabetic mice.

Chen SL, Hu ZY, Zuo GF, Li MH, Li B - BMC Cardiovasc Disord (2014)

Bottom Line: Our results showed that ivabradine treatment attenuated the expression and staining score of matrix metalloproteinase (MMP)-2, induced the dephosphorylation of caspase 3, BAX and MMP-2, and enhanced the phosphorylation of NF-κB.Ivabradine treatment led to a significant improvement in cardiac function.Ivabradine significantly improved cardiac function by attenuating apoptosis and inhibiting the expression and activity of MMP-2 in diabetic mice, which underscored the novel clinical implications of ivabradine for diabetic patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, China. chmengx@126.com.

ABSTRACT

Background: Ivabradine (IVBD), a novel I(f)-channel inhibitor and specific heart rate-lowering agent, is known to have anti-oxidative activity that promotes endothelial function. However, the molecular mechanism through which IVBD acts on cardiac function has yet to be elucidated, especially in experimental diabetic animals.

Methods: For this reason, twenty diabetic mice were randomly assigned to IVBD-treated (10 mg/kg/day) and control (saline) groups. After a 3-month treatment, microarray assay was performed to identify differentia expressed genes, and cardiac function was measured by echocardiography, with subsequent immunohistochemistry analysis and western blotting.

Results: Our results showed that ivabradine treatment attenuated the expression and staining score of matrix metalloproteinase (MMP)-2, induced the dephosphorylation of caspase 3, BAX and MMP-2, and enhanced the phosphorylation of NF-κB. Ivabradine treatment led to a significant improvement in cardiac function.

Conclusion: Ivabradine significantly improved cardiac function by attenuating apoptosis and inhibiting the expression and activity of MMP-2 in diabetic mice, which underscored the novel clinical implications of ivabradine for diabetic patients.

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Western blot analysis of the phosphorylation of BAX. BAX was dephosphorylated significantly in the ivabradine group, compared with the control group.
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Fig5: Western blot analysis of the phosphorylation of BAX. BAX was dephosphorylated significantly in the ivabradine group, compared with the control group.

Mentions: Based on the results of the microarray, we investigated the phosphorylation of MMP-2 and several other proteins involved in apoptosis, including NF-κB, caspase 3 and BAX. Phosphorylation of caspase 3 and BAX was significantly reduced by ivabradine (Figure 4 and Figure 5), consistent with the increased phosphorylation of NF-κB after treatment by ivabradine (Figure 6). In line with the microarray analysis, MMP-2 phosphorylation was inhibited in ivabradine-treated rats (Figure 7) compared with the control group.Figure 4


I(f) current channel inhibitor (ivabradine) deserves cardioprotective effect via down-regulating the expression of matrix metalloproteinase (MMP)-2 and attenuating apoptosis in diabetic mice.

Chen SL, Hu ZY, Zuo GF, Li MH, Li B - BMC Cardiovasc Disord (2014)

Western blot analysis of the phosphorylation of BAX. BAX was dephosphorylated significantly in the ivabradine group, compared with the control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230832&req=5

Fig5: Western blot analysis of the phosphorylation of BAX. BAX was dephosphorylated significantly in the ivabradine group, compared with the control group.
Mentions: Based on the results of the microarray, we investigated the phosphorylation of MMP-2 and several other proteins involved in apoptosis, including NF-κB, caspase 3 and BAX. Phosphorylation of caspase 3 and BAX was significantly reduced by ivabradine (Figure 4 and Figure 5), consistent with the increased phosphorylation of NF-κB after treatment by ivabradine (Figure 6). In line with the microarray analysis, MMP-2 phosphorylation was inhibited in ivabradine-treated rats (Figure 7) compared with the control group.Figure 4

Bottom Line: Our results showed that ivabradine treatment attenuated the expression and staining score of matrix metalloproteinase (MMP)-2, induced the dephosphorylation of caspase 3, BAX and MMP-2, and enhanced the phosphorylation of NF-κB.Ivabradine treatment led to a significant improvement in cardiac function.Ivabradine significantly improved cardiac function by attenuating apoptosis and inhibiting the expression and activity of MMP-2 in diabetic mice, which underscored the novel clinical implications of ivabradine for diabetic patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, China. chmengx@126.com.

ABSTRACT

Background: Ivabradine (IVBD), a novel I(f)-channel inhibitor and specific heart rate-lowering agent, is known to have anti-oxidative activity that promotes endothelial function. However, the molecular mechanism through which IVBD acts on cardiac function has yet to be elucidated, especially in experimental diabetic animals.

Methods: For this reason, twenty diabetic mice were randomly assigned to IVBD-treated (10 mg/kg/day) and control (saline) groups. After a 3-month treatment, microarray assay was performed to identify differentia expressed genes, and cardiac function was measured by echocardiography, with subsequent immunohistochemistry analysis and western blotting.

Results: Our results showed that ivabradine treatment attenuated the expression and staining score of matrix metalloproteinase (MMP)-2, induced the dephosphorylation of caspase 3, BAX and MMP-2, and enhanced the phosphorylation of NF-κB. Ivabradine treatment led to a significant improvement in cardiac function.

Conclusion: Ivabradine significantly improved cardiac function by attenuating apoptosis and inhibiting the expression and activity of MMP-2 in diabetic mice, which underscored the novel clinical implications of ivabradine for diabetic patients.

Show MeSH