Research

Publications

Below you can find a list of our published research.

103 results

eLife, Volume 9, 08 June 2020 Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating. Majumder R, De Coster T, Kudryashova N, Verkerk AO, Kazbanov IV, Ördög B, Harlaar N, Wilders R, de Vries AA, Ypey DL, Panfilov AV, Pijnappels DA

Homeostatic regulation protects organisms against hazardous physiological changes. However, such regulation is limited in certain organs and associated biological processes. For example, the heart fails to self-restore its normal electrical activity once disturbed, as with sustained arrhythmias. Here we present proof-of-concept of a biological self-restoring system that allows automatic detection and correction of such abnormal excitation rhythms. For the heart, its realization involves the inte... Abstract

Circulation research, 06 April 2020 Identification of Functional Variant Enhancers Associated with Atrial Fibrillation. van Ouwerkerk AF, Bosada F, Liu J, Zhang J, van Duijvenboden K, Chaffin M, Tucker N, Pijnappels DA, Ellinor PT, Barnett P, de Vries AA, Christoffels VM

Rationale: Genome-wide association studies (GWAS) have identified a large number of common variants (single nucleotide polymorphisms) associated with atrial fibrillation (AF). These variants are located mainly in non-coding regions of the genome and likely include variants that modulate the function of transcriptional regulatory elements (REs) such as enhancers. However, the actual REs modulated by variants as well as the target genes of such REs remain to be identified. Thus, the biological mec... Abstract

Frontiers in cardiovascular medicine, Volume 7, 31 March 2020, Pages 43 Multicellular In vitro Models of Cardiac Arrhythmias: Focus on Atrial Fibrillation. van Gorp PRR, Trines SA, Pijnappels DA, de Vries AAF

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice with a large socioeconomic impact due to its associated morbidity, mortality, reduction in quality of life and health care costs. Currently, antiarrhythmic drug therapy is the first line of treatment for most symptomatic AF patients, despite its limited efficacy, the risk of inducing potentially life-threating ventricular tachyarrhythmias as well as other side effects. Alternative, in-hospital treatment modalitie... Abstract

Journal of applied physiology (Bethesda, Md. : 1985), Volume 128, Issue 3, 30 January 2020, Pages 545-553 The proarrhythmic features of pathological cardiac hypertrophy in neonatal rat ventricular cardiomyocyte cultures. Neshati Z, Schalij MJ, de Vries AAF

Different factors may trigger arrhythmias in diseased hearts, including fibrosis, cardiomyocyte hypertrophy, hypoxia, and inflammation. This makes it difficult to establish the relative contribution of each of them to the occurrence of arrhythmias. Accordingly, in this study, we used an in vitro model of pathological cardiac hypertrophy (PCH) to investigate its proarrhythmic features and the underlying mechanisms independent of fibrosis or other PCH-related processes. Neonatal rat ventricular ca... Abstract

Cited 7 times since 2019 (4.9 per year) source: Scopus

Science translational medicine, Volume 11, Issue 481, 01 February 2019 An automated hybrid bioelectronic system for autogenous restoration of sinus rhythm in atrial fibrillation. Nyns ECA, Poelma RH, Volkers L, Plomp JJ, Bart CI, Kip AM, van Brakel TJ, Zeppenfeld K, Schalij MJ, Zhang GQ, de Vries AAF, Pijnappels DA

Because of suboptimal therapeutic strategies, restoration of sinus rhythm in symptomatic atrial fibrillation (AF) often requires in-hospital delivery of high-voltage shocks, thereby precluding ambulatory AF termination. Continuous, rapid restoration of sinus rhythm is desired given the recurring and progressive nature of AF. Here, we present an automated hybrid bioelectronic system for shock-free termination of AF that enables the heart to act as an electric current generator for autogenous rest... Abstract

Cited 4 times since 2018 (2.5 per year) source: Scopus

Cardiovascular research, Volume 114, Issue 14, 01 December 2018, Pages 1848-1859 Generation and primary characterization of iAM-1, a versatile new line of conditionally immortalized atrial myocytes with preserved cardiomyogenic differentiation capacity. Liu J, Volkers L, Jangsangthong W, Bart CI, Engels MC, Zhou G, Schalij MJ, Ypey DL, Pijnappels DA, de Vries AAF

Aims:The generation of homogeneous cardiomyocyte populations from fresh tissue or stem cells is laborious and costly. A potential solution to this problem would be to establish lines of immortalized cardiomyocytes. However, as proliferation and (terminal) differentiation of cardiomyocytes are mutually exclusive processes, their permanent immortalization causes loss of electrical and mechanical functions. We therefore aimed at developing conditionally immortalized atrial myocyte (iAM) lines allow... Abstract

Cited 5 times since 2018 (2.8 per year) source: Scopus

eLife, Volume 7, 27 September 2018 Optogenetics enables real-time spatiotemporal control over spiral wave dynamics in an excitable cardiac system. Majumder R, Feola I, Teplenin AS, de Vries AA, Panfilov AV, Pijnappels DA

Propagation of non-linear waves is key to the functioning of diverse biological systems. Such waves can organize into spirals, rotating around a core, whose properties determine the overall wave dynamics. Theoretically, manipulation of a spiral wave core should lead to full spatiotemporal control over its dynamics. However, this theory lacks supportive evidence (even at a conceptual level), making it thus a long-standing hypothesis. Here, we propose a new phenomenological concept that involves a... Abstract

Cited 3 times since 2018 (1.3 per year) source: Scopus

Journal of cellular biochemistry, Volume 119, Issue 7, 10 April 2018, Pages 6146-6153 Cardiomyogenic differentiation of human adipose-derived mesenchymal stem cells transduced with Tbx20-encoding lentiviral vectors. Neshati V, Mollazadeh S, Fazly Bazzaz BS, de Vries AA, Mojarrad M, Naderi-Meshkin H, Neshati Z, Kerachian MA

Ischemic heart disease often results in myocardial infarction and is the leading cause of mortality and morbidity worldwide. Improvement in the function of infarcted myocardium is a main purpose of cardiac regenerative medicine. One possible way to reach this goal is via stem cell therapy. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types but display limited cardiomyogenic differentiation potential. Members of the T-box family of tran... Abstract

Circulation. Arrhythmia and electrophysiology, Volume 11, Issue 2, 01 February 2018, Pages e006130 Response by Feola et al to Letter Regarding Article, "Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers". Feola I, Volkers L, Majumder R, Teplenin A, Schalij MJ, Panfilov AV, de Vries AAF, Pijnappels DA

Abstract

Cited 10 times since 2017 (3.7 per year) source: EuropePMC

Circulation. Arrhythmia and electrophysiology, Volume 10, Issue 11, 01 November 2017 Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers. Feola I, Volkers L, Majumder R, Teplenin A, Schalij MJ, Panfilov AV, de Vries AAF, Pijnappels DA

BACKGROUND:Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers. METHODS AND RESU... Abstract

Cited 30 times since 2017 (9.9 per year) source: Scopus

European heart journal, Volume 38, Issue 27, 01 July 2017, Pages 2132-2136 Optogenetic termination of ventricular arrhythmias in the whole heart: towards biological cardiac rhythm management. Nyns ECA, Kip A, Bart CI, Plomp JJ, Zeppenfeld K, Schalij MJ, de Vries AAF, Pijnappels DA

Current treatments of ventricular arrhythmias rely on modulation of cardiac electrical function through drugs, ablation or electroshocks, which are all non-biological and rather unspecific, irreversible or traumatizing interventions. Optogenetics, however, is a novel, biological technique allowing electrical modulation in a specific, reversible and trauma-free manner using light-gated ion channels. The aim of our study was to investigate optogenetic termination of ventricular arrhythmias in the... Abstract

Cited 8 times since 2017 (2.4 per year) source: Scopus

Cardiovascular research, Volume 113, Issue 3, 01 March 2017, Pages 354-366 Optogenetic manipulation of anatomical re-entry by light-guided generation of a reversible local conduction block. Watanabe M, Feola I, Majumder R, Jangsangthong W, Teplenin AS, Ypey DL, Schalij MJ, Zeppenfeld K, de Vries AA, Pijnappels DA

Aims:Anatomical re-entry is an important mechanism of ventricular tachycardia, characterized by circular electrical propagation in a fixed pathway. It's current investigative and therapeutic approaches are non-biological, rather unspecific (drugs), traumatizing (electrical shocks), or irreversible (ablation). Optogenetics is a new biological technique that allows reversible modulation of electrical function with unmatched spatiotemporal precision using light-gated ion channels. We therefore inve... Abstract

Cited 31 times since 2016 (8.6 per year) source: Scopus

EMBO molecular medicine, Volume 8, Issue 12, 01 December 2016, Pages 1390-1408 TECRL, a new life-threatening inherited arrhythmia gene associated with overlapping clinical features of both LQTS and CPVT. Devalla HD, Gélinas R, Aburawi EH, Beqqali A, Goyette P, Freund C, Chaix MA, Tadros R, Jiang H, Le Béchec A, Monshouwer-Kloots JJ, Zwetsloot T, Kosmidis G, Latour F, Alikashani A, Hoekstra M, Schlaepfer J, Mummery CL, Stevenson B, Kutalik Z, de Vries AA, Rivard L, Wilde AA, Talajic M, Verkerk AO, Al-Gazali L, Rioux JD, Bhuiyan ZA, Passier R

Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole-exome sequencing (WES) was carried out on patients from three different families that presented with life-threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Arg196Gln), which encodes the trans-2,3-enoyl-CoA reductase-like protein. Both patients had cardiac arrest, stress-induced atrial and ventricular t... Abstract

Cited 16 times since 2016 (3.8 per year) source: Scopus

Scientific reports, Volume 6, 13 April 2016, Pages 24334 Islands of spatially discordant APD alternans underlie arrhythmogenesis by promoting electrotonic dyssynchrony in models of fibrotic rat ventricular myocardium. Majumder R, Engels MC, de Vries AA, Panfilov AV, Pijnappels DA

Fibrosis and altered gap junctional coupling are key features of ventricular remodelling and are associated with abnormal electrical impulse generation and propagation. Such abnormalities predispose to reentrant electrical activity in the heart. In the absence of tissue heterogeneity, high-frequency impulse generation can also induce dynamic electrical instabilities leading to reentrant arrhythmias. However, because of the complexity and stochastic nature of such arrhythmias, the combined effect... Abstract

Cited 7 times since 2016 (1.6 per year) source: EuropePMC

Circulation. Arrhythmia and electrophysiology, Volume 9, Issue 4, 01 April 2016, Pages e003439 Allosteric Modulation of Kv11.1 (hERG) Channels Protects Against Drug-Induced Ventricular Arrhythmias. Yu Z, Liu J, van Veldhoven JP, IJzerman AP, Schalij MJ, Pijnappels DA, Heitman LH, de Vries AA

Ventricular arrhythmias as a result of unintentional blockade of the Kv11.1 (hERG [human ether-à-go-go-related gene]) channel are a major safety concern in drug development. In past years, several highly prescribed drugs have been withdrawn for their ability to cause such proarrhythmia. Here, we investigated whether the proarrhythmic risk of existing drugs could be reduced by Kv11.1 allosteric modulators.Using [(3)H]dofetilide-binding assays with membranes of human Kv11.1-expressing human embry... Abstract

Cited 4 times since 2016 (0.9 per year) source: Scopus

Methods in molecular biology (Clifton, N.J.), Volume 1408, 01 January 2016, Pages 319-331 Optogenetic Engineering of Atrial Cardiomyocytes. Feola I, Teplenin A, de Vries AA, Pijnappels DA

Optogenetics is emerging in the cardiology field as a new strategy to explore biological functions through the use of light-sensitive proteins and dedicated light sources. For example, this technology allows modification of the electrophysiological properties of cardiac muscle cells with superb spatiotemporal resolution and quantitative control. In this chapter, the optogenetic modification of atrial cardiomyocytes (aCMCs) from 2-day-old Wistar rats using lentiviral vector (LV) technology and th... Abstract

Cited 3 times since 2015 (0.6 per year) source: Scopus

Scientific reports, Volume 5, 21 October 2015, Pages 15187 Constitutively Active Acetylcholine-Dependent Potassium Current Increases Atrial Defibrillation Threshold by Favoring Post-Shock Re-Initiation. Bingen BO, Askar SF, Neshati Z, Feola I, Panfilov AV, de Vries AA, Pijnappels DA

Electrical cardioversion (ECV), a mainstay in atrial fibrillation (AF) treatment, is unsuccessful in up to 10-20% of patients. An important aspect of the remodeling process caused by AF is the constitutive activition of the atrium-specific acetylcholine-dependent potassium current (IK,ACh → IK,ACh-c), which is associated with ECV failure. This study investigated the role of IK,ACh-c in ECV failure and setting the atrial defibrillation threshold (aDFT) in optically mapped neonatal rat cardi... Abstract

Cited 3 times since 2015 (0.6 per year) source: Scopus

Cardiovascular research, Volume 107, Issue 4, 03 July 2015, Pages 601-612 Forced fusion of human ventricular scar cells with cardiomyocytes suppresses arrhythmogenicity in a co-culture model. Engels MC, Askar SF, Jangsangthong W, Bingen BO, Feola I, Liu J, Majumder R, Versteegh MI, Braun J, Klautz RJ, Ypey DL, De Vries AA, Pijnappels DA

Fibrosis increases arrhythmogenicity in myocardial tissue by causing structural and functional disruptions in the cardiac syncytium. Forced fusion of fibroblastic cells with adjacent cardiomyocytes may theoretically resolve these disruptions. Therefore, the electrophysiological effects of such electrical and structural integration of fibroblastic cells into a cardiac syncytium were studied.Human ventricular scar cells (hVSCs) were transduced with lentiviral vectors encoding enhanced green fluore... Abstract

World journal of experimental medicine, Volume 5, Issue 2, 20 May 2015, Pages 140-153 Barriers in contribution of human mesenchymal stem cells to murine muscle regeneration. de la Garza-Rodea AS, Boersma H, Dambrot C, de Vries AA, van Bekkum DW, Knaän-Shanzer S

AIM: To study regeneration of damaged human and murine muscle implants and the contribution of added xenogeneic mesenchymal stem cells (MSCs). METHODS: Minced human or mouse skeletal muscle tissues were implanted together with human or mouse MSCs subcutaneously on the back of non-obese diabetic/severe combined immunodeficient mice. The muscle tissues (both human and murine) were minced with scalpels into small pieces (< 1 mm(3)) and aliquoted in portions of 200 mm(3). These portions were either... Abstract

Cited 7 times since 2015 (1.3 per year) source: EuropePMC

Cell transplantation, Volume 24, Issue 12, 23 January 2015, Pages 2463-2478 Human Placenta-Derived Multipotent Cells (hPDMCs) Modulate Cardiac Injury: From Bench to Small and Large Animal Myocardial Ischemia Studies. Liu YH, Peng KY, Chiu YW, Ho YL, Wang YH, Shun CT, Huang SY, Lin YS, de Vries AA, Pijnappels DA, Lee NT, Yen BL, Yen ML

Cardiovascular disease is the leading cause of death globally, and stem cell therapy remains one of the most promising strategies for regeneration or repair of the damaged heart. We report that human placenta-derived multipotent cells (hPDMCs) can modulate cardiac injury in small and large animal models of myocardial ischemia (MI) and elucidate the mechanisms involved. We found that hPDMCs can undergo in vitro cardiomyogenic differentiation when cocultured with mouse neonatal cardiomyocytes. Mor... Abstract