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

Research Article

Guang-Feng Zuo¹  Shao-Liang Chen¹  Zuo-Ying Hu²  Bin Li³  Ming-Hui Li⁴ 

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

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

DOI  :  10.1186/1471-2261-14-150

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

来源: Springer

【 摘 要 】

BackgroundIvabradine (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.MethodsFor 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.ResultsOur 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.ConclusionIvabradine 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】

CC BY   
© Chen et al.; licensee BioMed Central Ltd. 2014