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

BMC Cardiovascular Disorders

Bin Li³  Ming-Hui Li¹  Guang-Feng Zuo²  Zuo-Ying Hu⁴  Shao-Liang Chen² 

[1] Third Clinical Medical College, Nanjing Medical University, Nanjing, China;Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, China;Nanjing Medical University, Nanjing, China;Department of Cardiology, Nanjing Heart Center, Nanjing, China

关键词: Apoptosis;    Immunohistochemistry;    Signal pathway;    Microarray;    Gene;    Diabetes;   

Others  :  1088422
DOI  :  10.1186/1471-2261-14-150

 received in 2014-08-29, accepted in 2014-10-17,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Chen et al.; licensee BioMed Central Ltd.

【 图 表 】

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