Metoprolol protects cardiomyocytes in rabbit model of heart failure by regulating Cx43

Zhai, Hu; Dai, Wenyi; Wang, Yu

doi:10.3892/etm.2017.5590

Cited by 6 publications

(8 citation statements)

References 17 publications

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“…This pathway can recover gap junction communication, leading to improved conduction velocity. These changes ultimately reduce susceptibility to ventricular arrhythmias ( Zhou et al., 2017 ; Zhai et al., 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Anti‐Arrhythmic Effects of Linalool via Cx43 Expression in a Rat Model of Myocardial Infarction

Zhu

Zhang

et al. 2020

Front. Pharmacol.

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Background: Lavender is a traditional therapy for different heart symptoms including palpitation, which comprises an important symptom of cardiac arrhythmias. This experiment was designed to evaluate the antiarrhythmic effects of linalool using an experimental model of arrhythmia following myocardial infarction in rats. The underlying electrophysiological mechanism through cardiac connexin 43 (Cx43) expression was also investigated. Methods: Fifty male Sprague-Dawley rats were divided into five equal groups. The first group was considered as the normal control group; MI was induced by ligation of the left anterior descending artery (LAD) in the second group. The other three groups received metoprolol (100 mg/kg/day) or linalool (50 or 100 mg/kg/day) for seven days before LAD ligation. The arrhythmia score, isolated myocyte resting potential, histological changes, and cardiac Cx43 expression levels were evaluated. Results: In the MI group, there was a significant increase in the arrhythmia score but a marked decrease in resting membrane potential relative to the control; these changes were prevented by the administration of metoprolol or linalool. The histological changes were also minimized in the groups treated with these substances compared to the untreated MI group. The western blot and real-time PCR results showed that the protein expression of Cx43 in the infarct zone of the rat hearts was significantly higher in the MI groups receiving metoprolol or linalool compared with the untreated MI group. Conclusion: Linalool was shown to be able to dose-dependently decrease the incidence of arrhythmias in a rat model of myocardial infarction. We propose that the key mechanism behind this antiarrhythmic effect is probably the prevention of decreased Cx43 expression following MI.

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Section: Discussionmentioning

confidence: 99%

Anti‐Arrhythmic Effects of Linalool via Cx43 Expression in a Rat Model of Myocardial Infarction

Zhu

Zhang

et al. 2020

Front. Pharmacol.

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“…reduced or eliminated in the infarct zone and border zone after acute focal ischemia (14,15), and this effect is accompanied by Cx43 redistribution, which undermines the conduction velocity and the inhomogeneous anisotropy of cardiac conduction, causing severe ventricular arrhythmias (16,17). Cx43 remodeling plays a significant role in the pathogenesis and prognosis of ischemic arrhythmias, and interventions targeting Cx43 remodeling may reduce the occurrence of ventricular arrhythmias after MI.…”

Section: Discussionmentioning

confidence: 99%

Combination of HGF and IGF-1 promotes connexin 43 expression and improves ventricular arrhythmia after myocardial infarction through activating the MAPK/ERK and MAPK/p38 signaling pathways in a rat model

Yao¹,

Ke²,

Zhou³

et al. 2019

Cardiovasc. Diagn. Ther.

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Background: In this study, we hypothesized that the combination of hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) alters the expression of connexin 43 (Cx43) and results in a reduced frequency of induced ventricular arrhythmia in rats after myocardial infarction (MI) and explored the preliminary mechanisms involved. Methods: Cardiomyocytes were cultured in vitro in medium with PBS, HGF, IGF-1, GFs (HGF + IGF-1), HGF + p38 inhibitor, HGF + ERK inhibitor, IGF-1 + p38 inhibitor or IGF-1 + ERK inhibitor. The expression of Cx43 was tested by real-time PCR and Western blotting after 48 hours. MI was induced in 48 male Sprague-Dawley rats. The rats were randomly divided into four groups and received an injection of PBS, HGF, IGF-1 or GFs into the infarct border zone two weeks after MI. Six weeks after injection, the expression levels of Cx43 and programmed stimulation-induced ventricular arrhythmias were examined. Results: In vitro, the expression of Cx43 mRNA and the Cx43 protein in cardiomyocytes was higher in the HGF, IGF-1, and GFs groups than in the PBS group. GFs had a combinatorial effect on the Cx43 mRNA level but not on the Cx43 protein level. There was a significant reduction in Cx43 mRNA and Cx43 protein levels in the IGF-1 + p38 inhibitor group and IGF-1 + ERK inhibitor group compared to the IGF-1 group. In vivo, programmed stimulation significantly decreased the frequency of ventricular arrhythmia in the GFs, HGF and IGF-1 groups, and this effect was accompanied by increased immunohistochemical staining for Cx43, myocardial Cx43 protein levels and Cx43 mRNA levels in the infarct border zone of the left ventricle compared with those in the PBS group. The combinatorial effect of GFs on Cx43 expression was only observed at the mRNA level. Conclusions: Both HGF and IGF-1 enhanced the expression of Cx43 and improved induced ventricular arrhythmia in rats with MI. Both synergistic and antagonistic effects of HGF and IGF-1 were not observed. In addition, IGF-1 may function through the MAPK/p38 and ERK1/2 signaling pathways to regulate Cx43 expression.

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“…According to the theory of miRNA biology, miR‐1 may down‐regulate Cx43 by forming the RNA‐induced silencing complex. Several researches have reported that metoprolol improved Cx43 expression and changed its distribution . Jiang et al .…”

Section: Discussionmentioning

confidence: 99%

“…indicated that metoprolol was effective in reducing ventricular arrhythmias by lighting the decreased expression of Cx43 induced by MI. Similarly, Zhai et al . found that metoprolol can protect cardiomyocytes in the heart failure model, and the mechanism was possibly related to the up‐regulation of Cx43 in cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

“…[36,37] Jiang et al [36] indicated that metoprolol was effective in reducing ventricular arrhythmias by lighting the decreased expression of Cx43 induced by MI. Similarly, Zhai et al [37] found that metoprolol can protect cardiomyocytes in the heart failure model, and the mechanism was possibly related to the upregulation of Cx43 in cardiomyocytes. Our study confirmed that pretreatment of metoprolol significantly improved Cx43 expression via down-regulating miR-1 in acute period of MI.…”

Section: Discussionmentioning

confidence: 99%

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Metoprolol protects against myocardial infarction by inhibiting miR-1 expression in rats

Qin

Zhang

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives Metoprolol is regarded as a first‐line medicine for the treatment of myocardial infarction (MI). However, the underlying mechanisms remain largely unknown. This study aimed to investigate the involvement of miR‐1 in the pharmacological function of metoprolol. Methods In vivo MI model was established by left anterior descending coronary artery (LAD) ligation. The effects of metoprolol on infarct size and cardiac dysfunction were determined by triphenyltetrazolium chloride staining and cardiac echocardiography, respectively. In vitro oxidative stress cardiomyocyte model was established by H2O2 treatment. The effect of metoprolol on the expression of miR‐1 and connexin43 (Cx43) was quantified by real‐time PCR and western blot, respectively. The intercellular communication was evaluated by lucifer yellow dye diffusion. Key findings Left anterior descending ligation‐induced MI injury was markedly attenuated by metoprolol as shown by reduced infarct size and better cardiac function. Metoprolol reversed the up‐regulation of miR‐1 and down‐regulation of Cx43 in MI heart. Moreover, in H2O2‐stimulated cardiomyocytes, overexpression of miR‐1 abolished the effects of metoprolol on Cx43 up‐regulation and increased intercellular communication, indicating that miR‐1 may be a necessary mediator for the cardiac protective function of metoprolol. Conclusions Metoprolol relieves MI injury via suppression miR‐1, thus increasing its target protein Cx43 and improving intercellular communication.

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Metoprolol protects cardiomyocytes in rabbit model of heart failure by regulating Cx43

Cited by 6 publications

References 17 publications

Anti‐Arrhythmic Effects of Linalool via Cx43 Expression in a Rat Model of Myocardial Infarction

Anti‐Arrhythmic Effects of Linalool via Cx43 Expression in a Rat Model of Myocardial Infarction

Combination of HGF and IGF-1 promotes connexin 43 expression and improves ventricular arrhythmia after myocardial infarction through activating the MAPK/ERK and MAPK/p38 signaling pathways in a rat model

Metoprolol protects against myocardial infarction by inhibiting miR-1 expression in rats

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