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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.

Show MeSH
RNA denaturing agarose gel electrophoresis for ivabradine and control groups. Animals in the ivabradine group were numbered as 1–5 and as 11–15.
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Fig1: RNA denaturing agarose gel electrophoresis for ivabradine and control groups. Animals in the ivabradine group were numbered as 1–5 and as 11–15.

Mentions: The 28S and 18S ribosomal RNA bands should be fairly sharp, intense bands (size is dependent on the organism from which the RNA was obtained). The intensity of the upper band should be about twice that of the lower band. Smaller, more diffuse bands representing low molecular weight RNAs (tRNA and 5S ribosomal RNA) may be present. It is normal to see a diffuse smear of ethidium bromide staining material migrating between the 18S and 28S ribosomal bands, probably comprised of mRNA and other heterogeneous RNA species. DNA contamination of the RNA preparation (if present) will be evident as a high molecular weight smear or band migrating above the 28S ribosomal RNA band. Degradation of the RNA will be reflected by smearing of ribosomal RNA bands (Table 1, Figure 1).Table 1


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)

RNA denaturing agarose gel electrophoresis for ivabradine and control groups. Animals in the ivabradine group were numbered as 1–5 and as 11–15.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: RNA denaturing agarose gel electrophoresis for ivabradine and control groups. Animals in the ivabradine group were numbered as 1–5 and as 11–15.
Mentions: The 28S and 18S ribosomal RNA bands should be fairly sharp, intense bands (size is dependent on the organism from which the RNA was obtained). The intensity of the upper band should be about twice that of the lower band. Smaller, more diffuse bands representing low molecular weight RNAs (tRNA and 5S ribosomal RNA) may be present. It is normal to see a diffuse smear of ethidium bromide staining material migrating between the 18S and 28S ribosomal bands, probably comprised of mRNA and other heterogeneous RNA species. DNA contamination of the RNA preparation (if present) will be evident as a high molecular weight smear or band migrating above the 28S ribosomal RNA band. Degradation of the RNA will be reflected by smearing of ribosomal RNA bands (Table 1, Figure 1).Table 1

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