Ivabradine Ameliorates Cardiac Function in Heart Failure with Preserved and Reduced Ejection Fraction via Upregulation of miR-133a.
Ivabradine Ameliorates Cardiac Function in Heart Failure with Preserved and Reduced Ejection Fraction via Upregulation of miR-133a.
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伊伐布雷定通过上调 miR-133a 改善心力衰竭患者的心脏功能，并保留和降低射血分数
DOI：
10.1155/2021/1257283
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发表时间：
2021
影响因子：
--
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Shao S;Zhang Y;Gong M;Yang Q;Yuan M;Yuan M;Suo Y;Wang X;Li Y;Bao Q;Li G
心力衰竭（HF）是由心室充盈、血液射血或两者受损引起的临床综合征，根据左心室功能分为射血分数降低的HF（HFrEF）或射血分数保留的HF（HFpEF）。心脏纤维化导致左心室功能障碍并导致HF的发展。伊伐布雷定是一种If电流选择性特异性抑制剂，已显示可改善HF患者的预后。然而，伊伐布雷定对HFpEF和HFrEF心脏功能和纤维化的影响及其潜在机制尚不清楚。在本研究中，我们利用小鼠模型模拟HFpEF和HFrEF，并评价伊伐布雷定的治疗作用。通过给予小鼠不同剂量（10 mg/kg/d和20 mg/kg/d）伊伐布雷定治疗4周或8周，我们发现高剂量伊伐布雷定改善了HFpEF小鼠的心脏舒张功能，并改善了HFrEF小鼠的心脏舒张和收缩功能和室性心动过速发生率。此外，伊伐布雷定显著降低了小鼠心脏成纤维细胞的活化和心肌纤维化。从机制上讲，伊伐布雷定上调的microRNA-133 a靶向心脏成纤维细胞中的结缔组织生长因子和胶原蛋白1，可能有助于伊伐布雷定的保护作用。总之，我们的工作利用小鼠模型研究HFpEF和HFrEF，证明了伊伐布雷定在HFpEF和HFrEF中的保护作用，并阐明了潜在的潜在机制，为相关疾病提供了有效的策略。
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.
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