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

Freundt, Johanna K.; Frommeyer, Gerrit; Spieker, Tilmann; Wötzel, Fabian; Grotthoff, Jochen Schulze; Stypmann, Jörg; Hempel, Georg; Schäfers, Michael; Eckardt, Lars; Lange, Philipp

doi:10.1186/s40360-019-0294-x

Cited by 16 publications

(13 citation statements)

References 32 publications

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“…The underlying mechanism may be a dowmregulation of the Ito subunit, Kv4.3, the Ikr subunit, KCNH2 ,the Iks subunit, KCNQ1, and CX43. This is partially consist with previous research [26][27][28]. It can be explain that the mehtods used to induce CHF in previousstudy are different.…”

Section: Effect Of Ccm Treatment On Electrical Remolding In Heart Faiuresupporting

confidence: 80%

Cardiac contractility modulation regulates the structural and electrical remolding in chronic heart failure rabbit model

Zhang

Dang

Hao

et al. 2019

Preprint

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Background Chronic heart failure (CHF) is accompanied by complex changes in cardiac electrophysiology and functional properties of cardiomyocytes which cause the structural and electrical remodeling process. Cardiac contractility modulation (CCM) is a novel therapeutic method and has proven to be effective in improving cardiac function. This study evaluated the effects of CCM on structural and electrical remolding in a rabbit model of CHF. Methods Thirty rabbits were randomly divided into sham group, heart failure group and CCM group. CHF model was induced 12 weeks after trans aortic constriction by pressure unloading. Then cardiac contractility modulation was delivered to the myocardium lasting six hours per day for 4 weeks. Structural changes were assessed by hydroxyproline assay and picrosirius red staining. The QTc intervals, ventricular effective refractory period and the inducibility of ventricular tachycardia were measured by electrophysiological examination. Protein levels of CTGF, Gal-3, Kv4.3, KCNQ1, KCNH2 and CX43 were measured by western blot analysis. Results Our study revealed that CHF rabbits developed significant prolonged QTc, ventricular effective refractory period and increased inducibility of ventricular tachycardia. Prominent myocardial fibrosis and increased levels of hydroxyproline content were observed in the heart failure group. Changes mentioned above can be suppressed with CCM therapy in CHF rabbits. The protein levels of CTGF, Gal-3, Kv4.3, KCNQ1, KCNH2 and CX43 significantly increased in the heart failure group, but these changes were prevented in the CCM group. Conclusions The present study demonstrated that CCM treatment prevented myocardial structural and electrical remolding in a rabbit model of CHF. The beneficial effect of CCM may be related to prevention of downregulation of the CTGF, Gal-3, Kv4.3, KCNQ1, KCNH2 and CX43. These findings provide experimental evidence for the clinical use of CCM in the treatment of HF.

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Section: Effect Of Ccm Treatment On Electrical Remolding In Heart Faiuresupporting

confidence: 80%

Cardiac contractility modulation regulates the structural and electrical remolding in chronic heart failure rabbit model

Zhang

Dang

Hao

et al. 2019

Preprint

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“…Both ADRA2C and ADRB1 are involved in the regulation of myocardial contractility, heart rate, and blood pressure [44]. KCNH2 and SCN5A are involved in the reconstruction of myocardial scaffold proteins [45,46]. NOS3 and NOS2 have superoxide metabolism, nitric oxide reaction, and regulation of arterial blood pressure [47].…”

Section: Discussionmentioning

confidence: 99%

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

Tao

Huang

Wang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Heart failure (HF), a clinical syndrome with a high incidence due to various reasons, is the advanced stage of most cardiovascular diseases. Huangqi is an effective treatment for cardiovascular disease, which has multitarget, multipathway functions. Therefore, we used network pharmacology to explore the molecular mechanism of Huangqi in treating HF. In this study, 21 compounds of Huangqi, which involved 407 targets, were obtained and reconfirmed using TCMSP and PubChem databases. Moreover, we used Cytoscape 3.7.1 to construct compound-target network and screened the top 10 compounds. 378 targets related to HF were obtained from CTD and GeneCards databases and HF-target network was constructed by Cytoscape 3.7.1. The 46 overlapping targets of HF and Huangqi were gotten by Draw Venn Diagram. STRING database was used to set up a protein-protein interaction network, and MCODE module and the top 5 targets with the highest degree for overlapping targets were obtained. GO analysis performed by Metascape indicated that the overlapping targets were mainly enriched in blood vessel development, reactive oxygen species metabolic process, response to wounding, blood circulation, and so on. KEGG analysis analyzed by ClueGO revealed that overlapping targets were mainly enriched in AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, c-type lectin receptor signaling pathway, relaxin signaling pathway, and so on. Finally, molecular docking showed that top 10 compounds of Huangqi also had good binding activities to important targets compared with digoxin, which was carried out in CB-Dock molecular docking server. In conclusion, Huangqi has potential effect on regulating overlapping targets and GE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, and so on to be a latent multitarget, multipathway treatment for HF.

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“…These recordings are known as monophasic action potentials (MAPs) and are routinely recorded from Langendorff perfused animal hearts to directly assess cardiac electrophysiology. Freundt et al (2019) (Franz, 1991;Tse et al, 2016).…”

Section: Monophasic and Transmembrane Action Potential Recordingsmentioning

confidence: 99%

Basic Research Approaches to Evaluate Cardiac Arrhythmia in Heart Failure and Beyond

et al. 2022

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Patients with heart failure often develop cardiac arrhythmias. The mechanisms and interrelations linking heart failure and arrhythmias are not fully understood. Historically, research into arrhythmias has been performed on affected individuals or in vivo (animal) models. The latter however is constrained by interspecies variation, demands to reduce animal experiments and cost. Recent developments in in vitro induced pluripotent stem cell technology and in silico modelling have expanded the number of models available for the evaluation of heart failure and arrhythmia. An agnostic approach, combining the modalities discussed here, has the potential to improve our understanding for appraising the pathology and interactions between heart failure and arrhythmia and can provide robust and validated outcomes in a variety of research settings. This review discusses the state of the art models, methodologies and techniques used in the evaluation of heart failure and arrhythmia and will highlight the benefits of using them in combination. Special consideration is paid to assessing the pivotal role calcium handling has in the development of heart failure and arrhythmia.

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

Cited by 16 publications

References 32 publications

Cardiac contractility modulation regulates the structural and electrical remolding in chronic heart failure rabbit model

Cardiac contractility modulation regulates the structural and electrical remolding in chronic heart failure rabbit model

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

Basic Research Approaches to Evaluate Cardiac Arrhythmia in Heart Failure and Beyond

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