Ivabradine Ameliorates Cardiac Function in Heart Failure with Preserved and Reduced Ejection Fraction via Upregulation of miR-133a
| Autor: | Guangping Li, Xinghua Wang, Qiankun Bao, Ming Yuan, Ya Suo, Qian Yang, Yue Zhang, Mengqi Gong, Ying Li, Shuai Shao, Meng Yuan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Cardiac function curve Aging medicine.medical_specialty Cardiotonic Agents Article Subject Systole Cardiac fibrosis Heart Ventricles Diastole Transfection Ventricular tachycardia Biochemistry Rats Sprague-Dawley Mice Ventricular Dysfunction Left Fibrosis Internal medicine medicine Animals Ivabradine Cells Cultured Heart Failure Ejection fraction QH573-671 business.industry Stroke Volume Cell Biology General Medicine Fibroblasts medicine.disease Rats Up-Regulation Mice Inbred C57BL Disease Models Animal MicroRNAs Treatment Outcome Animals Newborn Heart failure Cardiology business Cytology Signal Transduction Research Article medicine.drug |
| Zdroj: | Oxidative Medicine and Cellular Longevity, Vol 2021 (2021) Oxidative Medicine and Cellular Longevity |
| ISSN: | 1942-0900 |
| DOI: | 10.1155/2021/1257283 |
| Popis: | Heart failure (HF) is a clinical syndrome caused by impairment of ventricular filling, ejection of blood, or both and is categorized as HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF) based on left ventricular function. Cardiac fibrosis contributes to left ventricular dysfunction and leads to the development of HF. Ivabradine, an If current selective specific inhibitor, has been shown to improve the prognosis of patients with HF. However, the effects of ivabradine on cardiac function and fibrosis in HFpEF and HFrEF and the underlying mechanism remain unclear. In the present study, we utilized mouse models to mimic HFpEF and HFrEF and evaluated the therapeutic effects of ivabradine. By treating mice with different doses (10 mg/kg/d and 20 mg/kg/d) of ivabradine for 4 or 8 weeks, we found that a high dose of ivabradine improved cardiac diastolic function in HFpEF mice and ameliorated cardiac diastolic and systolic function and ventricular tachycardia incidence in HFrEF mice. Moreover, ivabradine significantly reduced the activation of cardiac fibroblasts and myocardial fibrosis in mice. Mechanistically, microRNA-133a, which was upregulated by ivabradine, targeted connective tissue growth factor and collagen 1 in cardiac fibroblasts and might contribute to the protective role of ivabradine. Together, our work utilized mouse models to study HFpEF and HFrEF, demonstrated the protective role of ivabradine in HFpEF and HFrEF, and elucidated the potential underlying mechanism, which provides an effective strategy for related diseases. |
| Databáze: | OpenAIRE |
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