Bisoprolol reverses down-regulation of potassium channel proteins in ventricular tissues of rabbits with heart failure

Li, Xi; Wang, Tingzhong; Han, Kihye; Zhuo, Xianlu; Lu, Qun; Ma, Aiqun

doi:10.1016/s1674-8301(11)60037-7

Cited by 7 publications

(4 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, the downregulation of the ERG ion channel KCNH2 in failing rabbit hearts might have contributed to the observed prolongation of MAPs. In contrast to our results, the expression of I to subunit Kv1.4 mRNA was significantly down-regulated in rabbits with heart failure [31]. Changes in Kv1.5 expression have been variable related to differences in underlying heart disease [32].…”

Section: Discussioncontrasting

confidence: 96%

“…Data on ERG expression in failing hearts has been inconsistent, few studies report a reduction of ERG expression in heart failure [30]. Li et al did not detect significant differences in mRNA ERG expression in the left ventricles among rabbits with heart failure [31]. In our study, the downregulation of the ERG ion channel KCNH2 in failing rabbit hearts might have contributed to the observed prolongation of MAPs.…”

Section: Discussioncontrasting

confidence: 48%

See 1 more Smart Citation

Histone deacetylase inhibition by Entinostat for the prevention of electrical and structural remodeling in heart failure

Freundt

Frommeyer

Spieker

et al. 2019

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

Background The development of heart failure is accompanied by complex changes in cardiac electrophysiology and functional properties of cardiomyocytes and fibroblasts. Histone deacetylase (HDAC) inhibitors hold great promise for the pharmaceutical therapy of several malignant diseases. Here, we describe novel effects of the class I HDAC inhibitor Entinostat on electrical and structural remodeling in an in vivo model of pacing induced heart failure. Methods Rabbits were implanted a pacemaker system, subjected to rapid ventricular pacing and treated with Entinostat or placebo, respectively. Following stimulation, rabbit hearts were explanted and subsequently subjected to electrophysiological studies and further immunohistological analyses of left ventricles. Results In vivo, rapid ventricular stimulation caused a significant prolongation of monophasic action potential duration compared to sham hearts (from 173 ± 26 ms to 250 ± 41 ms; cycle length 900 ms; p < 0.05) and an increased incidence of Early afterdepolarisations (+ 150%), while treatment with Entinostat in failing hearts could partially prevent this effect (from 250 ± 41 ms to 170 ± 53 ms, p < 0.05; reduction in EAD by 50%). Entinostat treatment partially restored KCNH2 and Cav1.3 gene expressions in failing hearts, and inhibited the development of cardiac fibrosis in vivo. Conclusion In a rabbit model of heart failure, Entinostat diminishes heart failure related prolongation of repolarization and partially restores KCNH2 and Cav1.3 expression. In addition, Entinostat exerts antifibrotic properties both in vitro and in vivo. Thus, Entinostat might be an interesting candidate for the pharmaceutical therapy of heart failure directed against structural and electrical remodeling. Electronic supplementary material The online version of this article (10.1186/s40360-019-0294-x) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussioncontrasting

confidence: 96%

Section: Discussioncontrasting

confidence: 48%

Histone deacetylase inhibition by Entinostat for the prevention of electrical and structural remodeling in heart failure

Freundt

Frommeyer

Spieker

et al. 2019

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

show abstract

“…Bisoprolol and metoprolol counteracted the decreased K v 4.3 expression and the concomitant reduction of I to in different HF animal models [ 24 , 25 ]. In our in vitro analysis, the incubation of transfected HEK cells with the respective betablockers did not affect expression levels of the respective K v 4.3 isoforms.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of the Betablockers Carvedilol, Metoprolol and Bisoprolol on Cardiac Kv4.3 (Ito) Channel Isoforms

Rahm,

Hackbarth,

Müller

et al. 2023

IJMS

View full text Add to dashboard Cite

Cardiac Kv4.3 channels contribute to the transient outward K+ current, Ito, during early repolarization of the cardiac action potential. Two different isoforms of Kv4.3 are present in the human ventricle and exhibit differential remodeling in heart failure (HF). Cardioselective betablockers are a cornerstone of HF with reduced ejection fraction therapy as well as ventricular arrhythmia treatment. In this study we examined pharmacological effects of betablockers on both Kv4.3 isoforms to explore their potential for isoform-specific therapy. Kv4.3 isoforms were expressed in Xenopus laevis oocytes and incubated with the respective betablockers. Dose-dependency and biophysical characteristics were examined. HEK 293T-cells were transfected with the two Kv4.3 isoforms and analyzed with Western blots. Carvedilol (100 µM) blocked Kv4.3 L by 77 ± 2% and Kv4.3 S by 67 ± 6%, respectively. Metoprolol (100 µM) was less effective with inhibition of 37 ± 3% (Kv4.3 L) and 35 ± 4% (Kv4.3 S). Bisoprolol showed no inhibitory effect. Current reduction was not caused by changes in Kv4.3 protein expression. Carvedilol inhibited Kv4.3 channels at physiologically relevant concentrations, affecting both isoforms. Metoprolol showed a weaker blocking effect and bisoprolol did not exert an effect on Kv4.3. Blockade of repolarizing Kv4.3 channels by carvedilol and metoprolol extend their pharmacological mechanism of action, potentially contributing beneficial antiarrhythmic effects in normal and failing hearts.

show abstract

“…Both, KCNE1 and KCNE4, function as modulators of KCNQ1 activity262728293031. Previous studies found elevated and reduced KCNE1 expression during HF424344. Interestingly, Mansén et al demonstrated that both, weaker and stronger KCNE1 expression results in reduced I Ks and APD prolongation, and that the correct ratio of KCNE1 to KCNQ1 is crucial for conducting a physiological I Ks current45.…”

Section: Discussionmentioning

confidence: 99%

miR-19b Regulates Ventricular Action Potential Duration in Zebrafish

Benz

Kossack

Auth

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Sudden cardiac death due to ventricular arrhythmias often caused by action potential duration (APD) prolongation is a common mode of death in heart failure (HF). microRNAs, noncoding RNAs that fine tune gene expression, are frequently dysregulated during HF, suggesting a potential involvement in the electrical remodeling process accompanying HF progression. Here, we identified miR-19b as an important regulator of heart function. Zebrafish lacking miR-19b developed severe bradycardia and reduced cardiac contractility. miR-19b deficient fish displayed increased sensitivity to AV-block, a characteristic feature of long QT syndrome in zebrafish. Patch clamp experiments from whole hearts showed that miR-19b deficient zebrafish exhibit significantly prolonged ventricular APD caused by impaired repolarization. We found that miR-19b directly and indirectly regulates the expression of crucial modulatory subunits of cardiac ion channels, and thereby modulates AP duration and shape. Interestingly, miR-19b knockdown mediated APD prolongation can rescue a genetically induced short QT phenotype. Thus, miR-19b might represent a crucial modifier of the cardiac electrical activity, and our work establishes miR-19b as a potential candidate for human long QT syndrome.

show abstract

Bisoprolol reverses down-regulation of potassium channel proteins in ventricular tissues of rabbits with heart failure

Cited by 7 publications

References 26 publications

Histone deacetylase inhibition by Entinostat for the prevention of electrical and structural remodeling in heart failure

Histone deacetylase inhibition by Entinostat for the prevention of electrical and structural remodeling in heart failure

Differential Effects of the Betablockers Carvedilol, Metoprolol and Bisoprolol on Cardiac Kv4.3 (Ito) Channel Isoforms

miR-19b Regulates Ventricular Action Potential Duration in Zebrafish

Contact Info

Product

Resources

About