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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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Comparison of cardiac function between ivabradine and control groups. M-model echocardiography showed a significant increase of ventricular wall movement after ivabradine treatment (upper column); however, there was no significant difference in cardiac function in the control group (lower column).
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Fig2: Comparison of cardiac function between ivabradine and control groups. M-model echocardiography showed a significant increase of ventricular wall movement after ivabradine treatment (upper column); however, there was no significant difference in cardiac function in the control group (lower column).

Mentions: Indices of cardiac function were comparable between the ivabradine and control groups (Table 2 and Figure 2). Importantly, at the 3 month follow-up, IVSTs, LVDs, LVPWs, eject fraction (EF) and fractional shortening (FS) improved significantly in the ivabradine group (1.59 ± 0.03 mm, 1.65 ± 0.08 mm, 1.42 ± 0.09 mm, 75.7 ± 3.43% and 49.33 ± 3.01 %, respectively) compared with the control group (1.41 ± 0.21 mm, p = 0.022; 2.22 ± 0.53 mm, p = 0.017; 1.26 ± 0.14 mm, p = 0.032; 54.1 ± 8.3 %, p = 0.018; and 27.34 ± 4.87%, p < 0.001, respectively). Compared with the baseline measurements, at 3 months after administration of ivabradine, cardiac function was significantly improved with the exception of the left ventricular volume at end-diastole. However, there were no significant differences in echocardiographic measurements between the baseline and the 3 month follow-up in the control group.Table 2


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)

Comparison of cardiac function between ivabradine and control groups. M-model echocardiography showed a significant increase of ventricular wall movement after ivabradine treatment (upper column); however, there was no significant difference in cardiac function in the control group (lower column).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Comparison of cardiac function between ivabradine and control groups. M-model echocardiography showed a significant increase of ventricular wall movement after ivabradine treatment (upper column); however, there was no significant difference in cardiac function in the control group (lower column).
Mentions: Indices of cardiac function were comparable between the ivabradine and control groups (Table 2 and Figure 2). Importantly, at the 3 month follow-up, IVSTs, LVDs, LVPWs, eject fraction (EF) and fractional shortening (FS) improved significantly in the ivabradine group (1.59 ± 0.03 mm, 1.65 ± 0.08 mm, 1.42 ± 0.09 mm, 75.7 ± 3.43% and 49.33 ± 3.01 %, respectively) compared with the control group (1.41 ± 0.21 mm, p = 0.022; 2.22 ± 0.53 mm, p = 0.017; 1.26 ± 0.14 mm, p = 0.032; 54.1 ± 8.3 %, p = 0.018; and 27.34 ± 4.87%, p < 0.001, respectively). Compared with the baseline measurements, at 3 months after administration of ivabradine, cardiac function was significantly improved with the exception of the left ventricular volume at end-diastole. However, there were no significant differences in echocardiographic measurements between the baseline and the 3 month follow-up in the control group.Table 2

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