Ivabradine improved left ventricular function and pressure overload-induced cardiomyocyte apoptosis in a transverse aortic constriction mouse model

Yu, Yi-Hui; Hu, Zuo‐Ying; Liu, Bing; Wang, Zhimei; Chen, Shao‐Liang

doi:10.1007/s11010-018-3369-x

Cited by 19 publications

(14 citation statements)

References 46 publications

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“…Cardiomyocytes apoptosis increases when the heart is subjected to pressure overload or when cardiomyocytes are stimulated by Ang II (Yang et al, 2012;Yu, Hu, Li, Wang, & Chen, 2018). Galangin has been shown to modulate cell apoptosis (Tomar et al, 2017) (a key role in the transcription of profibrotic genes).…”

Section: Discussionmentioning

confidence: 99%

Galangin ameliorates cardiac remodeling via the MEK1/2–ERK1/2 and PI3K–AKT pathways

Wang

Huang

et al. 2019

Journal Cellular Physiology

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Cardiac remodeling is associated with inflammation and apoptosis. Galangin, as a natural flavonol, has the potent function of regulating inflammation and apoptosis, which are factors related to cardiac remodeling. Beginning 3 days after aortic banding (AB) or Sham surgery, mice were treated with galangin for 4 weeks. Cardiac remodeling was assessed according to echocardiographic parameters, histological analyses, and hypertrophy and fibrosis markers. Our results showed that galangin administration attenuated cardiac hypertrophy, dysfunction, and fibrosis response in AB mice and angiotensin II‐treated H9c2 cells. The inhibitory action of galangin in cardiac remodeling was mediated by MEK1/2–extracellular‐regulated protein kinases 1/2 (ERK1/2)–GATA4 and phosphoinositide 3‐kinase (PI3K)–protein kinase B (AKT)–glycogen synthase kinase 3β (GSK3β) activation. Furthermore, we found that galangin inhibited inflammatory response and apoptosis. Our findings suggest that galangin protects against cardiac remodeling through decreasing inflammatory responses and apoptosis, which are associated with inhibition of the MEK1/2–ERK1/2–GATA4 and PI3K–AKT–GSK3β signals.

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Section: Discussionmentioning

confidence: 99%

Galangin ameliorates cardiac remodeling via the MEK1/2–ERK1/2 and PI3K–AKT pathways

Wang

Huang

et al. 2019

Journal Cellular Physiology

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“…Heart disease animal models play an important role in studying these remodeling processes as well as in preclinical studies. The validity and accuracy of animal models are necessary for the mechanism study of HF and for new drug development as well (4,5).…”

Section: Introductionmentioning

confidence: 99%

Distinct Phenotypes Induced by Different Degrees of Transverse Aortic Constriction in C57BL/6N Mice

Deng

Kong

et al. 2021

Front. Cardiovasc. Med.

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The transverse aortic constriction (TAC) model surgery is a widely used disease model to study pressure overload–induced cardiac hypertrophy and heart failure in mice. The severity of adverse cardiac remodeling of the TAC model is largely dependent on the degree of constriction around the aorta, and the phenotypes of TAC are also different in different mouse strains. Few studies focus on directly comparing phenotypes of the TAC model with different degrees of constriction around the aorta, and no study compares the difference in C57BL/6N mice. In the present study, C57BL/6N mice aged 10 weeks were subjected to sham, 25G TAC, 26G TAC, and 27G TAC surgery for 4 weeks. We then analyzed the different phenotypes induced by 25G TAC, 26G TAC, and 27G TAC in c57BL/6N mice in terms of pressure gradient, cardiac hypertrophy, cardiac function, heart failure situation, survival condition, and cardiac fibrosis. All C57BL/6N mice subjected to TAC surgery developed significantly hypertrophy. Mice subjected to 27G TAC had severe cardiac dysfunction, severe cardiac fibrosis, and exhibited characteristics of heart failure at 4 weeks post-TAC. Compared with 27G TAC mice, 26G TAC mice showed a much milder response in cardiac dysfunction and cardiac fibrosis compared to 27G TAC, and a very small fraction of the 26G TAC group exhibited characteristics of heart failure. There was no obvious cardiac dysfunction, cardiac fibrosis, and characteristics of heart failure observed in 25G TAC mice. Based on our results, we conclude that the 25G TAC, 26G TAC, and 27G TAC induced distinct phenotypes in C57BL/6N mice.

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“…To investigate the effect of ivabradine on HFpEF, we treated mice at 4-weeks post-TAC with low-dose (10 mg/kg/d) [ 34 , 35 ] or high-dose (20 mg/kg/d) [ 34 , 35 ] ivabradine for another 4 weeks. We found that high-dose but not low-dose ivabradine significantly inhibited pressure overload-induced cardiac hypertrophy by reducing the cross-sectional areas of ventricular cardiomyocytes and the ratio of heart weight to tibial length (Figures 2(a) – 2(c) ).…”

Section: Resultsmentioning

confidence: 99%

Ivabradine Ameliorates Cardiac Function in Heart Failure with Preserved and Reduced Ejection Fraction via Upregulation of miR‐133a

Shao

Zhang

Gong

et al. 2021

Oxidative Medicine and Cellular Longevity

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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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Ivabradine improved left ventricular function and pressure overload-induced cardiomyocyte apoptosis in a transverse aortic constriction mouse model

Cited by 19 publications

References 46 publications

Galangin ameliorates cardiac remodeling via the MEK1/2–ERK1/2 and PI3K–AKT pathways

Galangin ameliorates cardiac remodeling via the MEK1/2–ERK1/2 and PI3K–AKT pathways

Distinct Phenotypes Induced by Different Degrees of Transverse Aortic Constriction in C57BL/6N Mice

Ivabradine Ameliorates Cardiac Function in Heart Failure with Preserved and Reduced Ejection Fraction via Upregulation of miR‐133a

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