Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43 (cx43)

Wu, Tao Cheng; Wu, Dan; Wu, Qinghua; Zou, Bing; Huang, Xiao; Cheng, Xiaoshu; Hong, Kui; Li, Ping

doi:10.1016/j.apjtm.2016.07.022

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…Lindsey et al ( 18 ) reported that the positive expression of Cx43 in model of myocardial infarction was significantly reduced, and the expression level of Cx43 protein was significantly lower than that of the control group, but the expression of Cx43 mRNA was not altered significantly. Results of this study showed that the distribution of Cx43 protein and the level of Cx43 mRNA and protein in rabbits after myocardial infarction were significantly decreased (P<0.05), suggesting that connexins were reconstructed after myocardial infarction, which is consistent with previous studies ( 19 ). After treatment with metoprolol, levels of Cx43 mRNA and protein in cardiomyocytes were significantly increased, suggesting that metoprolol can play a role in improving cardiac remodeling after myocardial infarction by regulating the expression of Cx43.…”

Section: Discussionsupporting

confidence: 91%

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

2017

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This study investigated the protective effect of metoprolol on cardiomyocytes in rabbits with heart failure and its possible mechanism. Sixty New Zealand white rabbits were randomly divided into infarction group and non-infarction group, 30 in each group. Myocardial infarction was constructed by ligation of anterior descending branch of coronary artery. Coronary artery threading without ligation after thoracotomy was performed for rabbits in non-infarction group. After model construction, rabbits in each group were further divided into control group (n=15) and metoprolol group (n=15), and fed with normal diet and normal diet + metoprolol. Animals were sacrificed 8 weeks later, and ventricular tissue around infarction area was collected. Expression of connexin 43 (Cx43) in myocardium was detected by immunohistochemistry. Expression of Cx43 protein and mRNA in each group was detected by western blot and reverse transcription PCR. The Cx43 protein was positively expressed in non-infarction group and was evenly distributed in intercellular space. Compared with non-infarction group, expression of Cx43 in infarction group was significantly decreased or even disappeared, while the decrease in expression level of Cx43 and the degree of dispersion were lower in metoprolol group than in control group. There was no significant difference in expression of level of Cx43 protein and mRNA between the subgroups of non-infarction group (P>0.05). In infarction group, expression level of Cx43 protein and mRNA in the metoprolol group were significantly higher than those in control group (P<0.05). The results showed that metoprolol can protect cardiomyocytes after myocardial infarction, and the possible mechanism is related to the regulation of Cx43 expression in cardiomyocytes.

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Section: Discussionsupporting

confidence: 91%

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

2017

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“…Reperfusion injury potentiates membrane permeability of cardiomyocytes and elevates myocardial injury marker levels in serum. The severity of myocardial tissue injury is correlated with CK-MB and cTnI levels [ 13 , 14 ]. Recent findings show that a variety of components from plants, such as malvidin, contribute to cardioprotective effects against isoproterenol-induced myocardial infarction in rats [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Pinocembrin Pretreatment on Connexin 43 (Cx43) Protein Expression After Rat Myocardial Ischemia-Reperfusion and Cardiac Arrhythmia

Zhang

et al. 2018

Med Sci Monit

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BackgroundCardiac infarction frequently leads to arrhythmia and ischemia/reperfusion (I/R) aggravates cardiac injury. Pinocembrin can resist cerebral ischemia and decrease cardiac infarction area. This study thus generated a rat myocardial I/R model to assess the effect on ventricular rhythm and expression of gap junction connexin (Cx43).Material/MethodsMale SD rats were randomly assigned into sham, model, and pinocembrin (30 mg/kg) pretreatment groups (N=15 each). The I/R model was generated by ligation of the left anterior descending coronary artery for 30 min. The pinocembrin group received intravenous injection 10 min before surgery. Heart rate (HR), mean artery pressure (MAP), rate pressure product (RPP), and arrhythmia were observed at 10 min before ischemia, 30 min after ischemia, and at 30, 60, and 120 min after reperfusion. ELISA was used to assess serum CK-MB and cTnI levels. Na+-K+ATPase and Ca+-Mg2+ATPase levels were quantified by spectrometry, followed by HE staining, IHC approach for Cx43 expression, and Western blot for Kir2.1 protein expression.ResultsModel rats had significantly lower HR, MAP, and RPP than in the sham group, and the pinocembrin pretreatment group had higher serum indexes. Arrhythmia index, CK-MB, and cTnI were higher in the model and pinocembrin groups, while Na+-K+ATPase, Ca+-Mg2+ATPase, Cx43, and Kir2.1 proteins were lower (p<0.05).ConclusionsPinocembrin alleviated ventricular arrhythmia in I/R rats via enhancing Na+-K+ATPase and Ca+-Mg2+ATPase activity and upregulating Cx43 and Kir2.1 protein expression.

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“…Correlation analysis showed that there was a significant positive correlation between CX43 and VFT after MI, that is, the expression of CX43 decreased, the VFT decreased, and the risk of arrhythmia increased. Since improving the expression of CX43 can effectively reduce the occurrence of arrhythmia after MI [ 18 ]. Therefore, further research on the molecular mechanism of regulating connexin could provide ideas for the prognostic treatment of MI.…”

Section: Discussionmentioning

confidence: 99%

Effect of WenXin KeLi on Improvement of Arrhythmia after Myocardial Infarction by Intervening PI3K-AKT-mTOR Autophagy Pathway

Yang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Myocardial infarction (MI) is an acute and serious cardiovascular disease. Arrhythmia after MI can lead to sudden cardiac death, which seriously affects the survival outcome of patients. WenXin KeLi is a Chinese patent medicine for the treatment of arrhythmia in a clinic, which can significantly improve symptoms of palpitation and play an important role in reducing the risk of arrhythmia after MI. In this study, we aimed to explore the pharmacological mechanism of WenXin KeLi in protecting the heart. Methods. The MI model was established by ligating the left coronary artery and the ventricular fibrillation threshold (VFT) was measured by electrical stimulation. The expression of connexin43 (CX43) and autophagy-related protein were measured by Western Blot, and correlation analysis was conducted to study the relationship between cardiac autophagy, CX43, and arrhythmia in rats after MI. The effects of WenXin KeLi on arrhythmia, cardiac structure, and function in MI rats were respectively observed by electrical stimulation, cardiac gross section, Masson staining, and cardiac ultrasound. The effects of WenXin KeLi on the expression of phosphoinositide 3 kinase-protein kinase B-mammalian targets of rapamycin (PI3K-AKT-mTOR) autophagy pathway and CX43 were observed by Western Blot. Results. After 4 weeks of MI, the VFT in the model group was significantly reduced, the expression levels of yeast ATG6 homolog (Beclin1), microtubule-associated protein 1A/1B-light chain 3 (LC3II/LC3I), and p-CX43 (S368) significantly increased, the expression of sequestosome-1(P62) and CX43 significantly decreased. LC3II/LC3I and Beclin1 expression were significantly negatively correlated with the VFT, and the expression of P62 and CX43 were significantly positively correlated with the VFT. LC3II/LC3I and Beclin1 expression were negatively correlated with CX43 expression, while P62 expression was positively correlated with CX43 expression. WenXin KeLi could significantly increase the VFT, reduce the deposition of collagen fibers, and increase the index levels of the left ventricular end-diastolic anterior wall (LVEDAW), interventricular septum end-diastolic (IVSED), left ventricular end-systolic anterior wall (LVESAW), interventricular septum end-systolic (IVSES), left ventricular end-diastolic posterior wall (LVEDPW), left ventricular end-systolic posterior wall (LVESPW), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and reduce the index levels of the left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). WenXin KeLi could increase the expression of CX43, P62, AKT, p-PI3K, p-AKT (308), p-AKT (473), and p-mTOR and decrease the expression of LC3II/LC3I and Beclin1. Conclusion. WenXin KeLi can activate the PI3K-AKT-mTOR signaling pathway, improve cardiac autophagy and Cx43 expression in rats after MI, reduce the risk of arrhythmia after MI, and play a cardioprotective role.

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Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43 (cx43)

Cited by 7 publications

References 18 publications

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

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

Effects of Pinocembrin Pretreatment on Connexin 43 (Cx43) Protein Expression After Rat Myocardial Ischemia-Reperfusion and Cardiac Arrhythmia

Effect of WenXin KeLi on Improvement of Arrhythmia after Myocardial Infarction by Intervening PI3K-AKT-mTOR Autophagy Pathway

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