ISSN 2149-2263 | E-ISSN 2149-2271
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Ivabradine promotes angiogenesis and reduces cardiac hypertrophy in mice with myocardial infarction [Anatol J Cardiol]
Anatol J Cardiol. 2018; 20(5): 266-272 | DOI: 10.14744/AnatolJCardiol.2018.46338

Ivabradine promotes angiogenesis and reduces cardiac hypertrophy in mice with myocardial infarction

Xiangqi Wu, Wei You, Zhiming Wu, Fei Ye, Shaoliang Chen
Division of Cardiology, Nanjing First Hospital, Nanjing Medical University; Nanjing-China

Objective: We investigated the underlying mechanism of ivabradine (IVA) in promoting angiogenesis and reducing cardiac hypertrophy in mice with myocardial infarction (MI).
Methods: Nineteen mice were randomly assigned into three groups as follows: sham group (10 ml/kg/day phosphate buffer saline (PBS), n=6), model group (MI and 10 ml/kg/day PBS, n=6) and IVA group (MI and 10 mg/kg/day IVA, n=7). All groups received an intragastric gavage for four weeks. Heart and body mass were measured. Cardiac function and heart rate were assessed by echocardiography and electrocardiography, respectively. The collagen deposition, area of cardiomyocytes, and number of capillaries were evaluated using Masson’s staining, anti-wheat germ agglutinin (WGA) staining, and platelet endothelial cell adhesion molecule-1 (CD31) staining, respectively. The protein kinase B (Akt)-endothelial nitric oxide synthase (eNOS) signaling and p-38 mitogen-activated protein kinase (MAPK) family in myocardium were determined by western blot.
Results: IVA treatment greatly improved cardiac dysfunction and suppressed cardiac hypertrophy at 4 weeks after MI (p<0.05). Heart rate and fibrotic area of IVA group declined notably compared to those of the model group (p<0.05). IVA administration substantially reduced cardiomyocyte size and increased capillary formation (p<0.05). Besides, IVA medication can enhance Akt-eNOS signaling and inhibit p38 MAPK phosphorylation in the heart of mice with MI (p<0.05).
Conclusion: IVA can perform two functions, the promotion of angiogenesis and the reduction of cardiac hypertrophy, both of which were closely associated with Akt-eNOS signaling activation and p38 MAPK inhibition.

Keywords: ivabradine, angiogenesis, myocardial infarction, mice

Xiangqi Wu, Wei You, Zhiming Wu, Fei Ye, Shaoliang Chen. Ivabradine promotes angiogenesis and reduces cardiac hypertrophy in mice with myocardial infarction. Anatol J Cardiol. 2018; 20(5): 266-272

Corresponding Author: Shaoliang Chen, China
Manuscript Language: English


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