Ivabradine Treatment Reduces Cardiomyocyte Apoptosis in a Murine Model of Chronic Viral Myocarditis
This study was designed to explore the effects of ivabradine on cardiomyocyte apoptosis in a murine model of chronic viral myocarditis (CVMC). Mice were inoculated intraperitoneally with Coxsackievirus B3 at days 1, 14, and 28, respectively. On day 42, the mice were gavaged with ivabradine for 30 da...
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00182/full |
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| author | Ge Li-Sha Liu Li Liu Li Zhou De-Pu Shi Zhe-Wei Gu Xiaohong Chen Guang-Yi Li Jia Lin Jia-Feng Chu Maoping Li Yue-Chun |
| author_facet | Ge Li-Sha Liu Li Liu Li Zhou De-Pu Shi Zhe-Wei Gu Xiaohong Chen Guang-Yi Li Jia Lin Jia-Feng Chu Maoping Li Yue-Chun |
| author_sort | Ge Li-Sha |
| collection | DOAJ |
| description | This study was designed to explore the effects of ivabradine on cardiomyocyte apoptosis in a murine model of chronic viral myocarditis (CVMC). Mice were inoculated intraperitoneally with Coxsackievirus B3 at days 1, 14, and 28, respectively. On day 42, the mice were gavaged with ivabradine for 30 days until the 72nd day. The heart of infected mice was dilated and a large number of interstitial fibroblasts infiltrated into the myocardium on day 42. Compared with the untreated CVMC mice, mice treated with ivabradine showed a significant reduction in heart rate and less impairment of left ventricular function on day 72. The positive apoptosis of myocardial cells in the untreated CVMC group was significantly higher than that of the normal group and was significantly reduced after treatment with ivabradine. The expression levels of Bax and Caspase-3 in the untreated CVMC group were significantly higher than those of the normal group and were apparently reduced in the ivabradine-treated group versus the untreated CVMC group. Bcl-2 showed a high expression in the normal group and low expression in the untreated CVMC group, but its expression level in the ivabradine-treated group were higher than that of the untreated CVMC group. These results indicate that ivabradine could attenuate the expression of Caspase-3 by downregulation of Bax and upregulation of Bcl-2 to prevent the deterioration of cardiac function resulting from ventricular myocyte loss by cardiomyocyte apoptosis. |
| first_indexed | 2024-04-13T18:59:13Z |
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| id | doaj.art-662970fa271c4106a3b88f565243cfb3 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T18:59:13Z |
| publishDate | 2018-03-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-662970fa271c4106a3b88f565243cfb32022-12-22T02:34:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-03-01910.3389/fphar.2018.00182280606Ivabradine Treatment Reduces Cardiomyocyte Apoptosis in a Murine Model of Chronic Viral MyocarditisGe Li-Sha0Liu Li1Liu Li2Zhou De-Pu3Shi Zhe-Wei4Gu Xiaohong5Chen Guang-Yi6Li Jia7Lin Jia-Feng8Chu Maoping9Li Yue-Chun10Department of Pediatric Emergency, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaChildren’s Heart Center and Department of Pediatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaChildren’s Heart Center and Department of Pediatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaThis study was designed to explore the effects of ivabradine on cardiomyocyte apoptosis in a murine model of chronic viral myocarditis (CVMC). Mice were inoculated intraperitoneally with Coxsackievirus B3 at days 1, 14, and 28, respectively. On day 42, the mice were gavaged with ivabradine for 30 days until the 72nd day. The heart of infected mice was dilated and a large number of interstitial fibroblasts infiltrated into the myocardium on day 42. Compared with the untreated CVMC mice, mice treated with ivabradine showed a significant reduction in heart rate and less impairment of left ventricular function on day 72. The positive apoptosis of myocardial cells in the untreated CVMC group was significantly higher than that of the normal group and was significantly reduced after treatment with ivabradine. The expression levels of Bax and Caspase-3 in the untreated CVMC group were significantly higher than those of the normal group and were apparently reduced in the ivabradine-treated group versus the untreated CVMC group. Bcl-2 showed a high expression in the normal group and low expression in the untreated CVMC group, but its expression level in the ivabradine-treated group were higher than that of the untreated CVMC group. These results indicate that ivabradine could attenuate the expression of Caspase-3 by downregulation of Bax and upregulation of Bcl-2 to prevent the deterioration of cardiac function resulting from ventricular myocyte loss by cardiomyocyte apoptosis.https://www.frontiersin.org/article/10.3389/fphar.2018.00182/fullcoxsackieviruschronic viral myocarditisheart rateivabradinecardiomyocyte apoptosis |
| spellingShingle | Ge Li-Sha Liu Li Liu Li Zhou De-Pu Shi Zhe-Wei Gu Xiaohong Chen Guang-Yi Li Jia Lin Jia-Feng Chu Maoping Li Yue-Chun Ivabradine Treatment Reduces Cardiomyocyte Apoptosis in a Murine Model of Chronic Viral Myocarditis Frontiers in Pharmacology coxsackievirus chronic viral myocarditis heart rate ivabradine cardiomyocyte apoptosis |
| title | Ivabradine Treatment Reduces Cardiomyocyte Apoptosis in a Murine Model of Chronic Viral Myocarditis |
| title_full | Ivabradine Treatment Reduces Cardiomyocyte Apoptosis in a Murine Model of Chronic Viral Myocarditis |
| title_fullStr | Ivabradine Treatment Reduces Cardiomyocyte Apoptosis in a Murine Model of Chronic Viral Myocarditis |
| title_full_unstemmed | Ivabradine Treatment Reduces Cardiomyocyte Apoptosis in a Murine Model of Chronic Viral Myocarditis |
| title_short | Ivabradine Treatment Reduces Cardiomyocyte Apoptosis in a Murine Model of Chronic Viral Myocarditis |
| title_sort | ivabradine treatment reduces cardiomyocyte apoptosis in a murine model of chronic viral myocarditis |
| topic | coxsackievirus chronic viral myocarditis heart rate ivabradine cardiomyocyte apoptosis |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.00182/full |
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