Publications
Below you can find a list of our published research.
Below you can find a list of our published research.
110 results
Cardiovascular research, Volume 120, Issue 3, 1 1 2024, Pages 249-261 'Trapped re-entry' as source of acute focal atrial arrhythmias. De Coster T, Teplenin AS, Feola I, Bart CI, Ramkisoensing AA, den Ouden BL, Ypey DL, Trines SA, Panfilov AV, Zeppenfeld K, de Vries AAF, Pijnappels DA
Aims: Diseased atria are characterized by functional and structural heterogeneities, adding to abnormal impulse generation and propagation. These heterogeneities are thought to lie at the origin of fractionated electrograms recorded during sinus rhythm (SR) in atrial fibrillation (AF) patients and are assumed to be involved in the onset and perpetuation (e.g. by re-entry) of this disorder. The underlying mechanisms, however, remain incompletely understood. Here, we tested whether regions of dens... Abstract
Computers in biology and medicine, Volume 169, 3 1 2024, Pages 107949 Fast creation of data-driven low-order predictive cardiac tissue excitation models from recorded activation patterns. Kabus D, De Coster T, de Vries AAF, Pijnappels DA, Dierckx H
Excitable systems give rise to important phenomena such as heat waves, epidemics and cardiac arrhythmias. Understanding, forecasting and controlling such systems requires reliable mathematical representations. For cardiac tissue, computational models are commonly generated in a reaction-diffusion framework based on detailed measurements of ionic currents in dedicated single-cell experiments. Here, we show that recorded movies at the tissue-level of stochastic pacing in a single variable are suff... Abstract
Cell reports methods, Volume 3, Issue 12, 11 2 2023, Pages 100671 Opto-electronic feedback control of membrane potential for real-time control of action potentials. Ördög B, De Coster T, Dekker SO, Bart CI, Zhang J, Boink GJJ, Bax WH, Deng S, den Ouden BL, de Vries AAF, Pijnappels DA
To unlock new research possibilities by acquiring control of action potential (AP) morphologies in excitable cells, we developed an opto-electronic feedback loop-based system integrating cellular electrophysiology, real-time computing, and optogenetic approaches and applied it to monolayers of heart muscle cells. This allowed accurate restoration and preservation of cardiac AP morphologies in the presence of electrical perturbations of different origin in an unsupervised, self-regulatory manner,... Abstract
Cited 3 times since 2023 (3.5 per year) source: EuropePMC
Journal of internal medicine, Volume 294, Issue 3, 21 3 2023, Pages 347-357 Light transmittance in human atrial tissue and transthoracic illumination in rats support translatability of optogenetic cardioversion of atrial fibrillation. Nyns ECA, Portero V, Deng S, Jin T, Harlaar N, Bart CI, van Brakel TJ, Palmen M, Hjortnaes J, Ramkisoensing AA, Zhang GQ, Poelma RH, Ördög B, de Vries AAF, Pijnappels DA
Background: Optogenetics could offer a solution to the current lack of an ambulatory method for the rapid automated cardioversion of atrial fibrillation (AF), but key translational aspects remain to be studied. Objective: To investigate whether optogenetic cardioversion of AF is effective in the aged heart and whether sufficient light penetrates the human atrial wall. Methods: Atria of adult and aged rats were optogenetically modified to express light-gated ion channels (i.e., red-activatable ch... Abstract
Cited 5 times since 2022 (2.7 per year) source: EuropePMC
Cardiovascular research, Volume 118, Issue 10, 1 1 2022, Pages 2293-2303 Optical ventricular cardioversion by local optogenetic targeting and LED implantation in a cardiomyopathic rat model. Nyns ECA, Jin T, Fontes MS, van den Heuvel T, Portero V, Ramsey C, Bart CI, Zeppenfeld K, Schalij MJ, van Brakel TJ, Ramkisoensing AA, Zhang G, Poelma RH, Ördög B, de Vries AAF, Pijnappels DA
Aims: Ventricular tachyarrhythmias (VTs) are common in the pathologically remodelled heart. These arrhythmias can be lethal, necessitating acute treatment like electrical cardioversion to restore normal rhythm. Recently, it has been proposed that cardioversion may also be realized via optically controlled generation of bioelectricity by the arrhythmic heart itself through optogenetics and therefore without the need of traumatizing high-voltage shocks. However, crucial mechanistic and translation... Abstract
Cited 2 times since 2022 (1 per year) source: EuropePMC
Circulation research, Volume 131, Issue 1, 19 3 2022, Pages 24-41 Sbk2, a Newly Discovered Atrium-Enriched Regulator of Sarcomere Integrity. van Gorp PRR, Zhang J, Liu J, Tsonaka R, Mei H, Dekker SO, Bart CI, De Coster T, Post H, Heck AJR, Schalij MJ, Atsma DE, Pijnappels DA, de Vries AAF
Background: Heart development relies on tight spatiotemporal control of cardiac gene expression. Genes involved in this intricate process have been identified using animals and pluripotent stem cell-based models of cardio(myo)genesis. Recently, the repertoire of cardiomyocyte differentiation models has been expanded with iAM-1, a monoclonal line of conditionally immortalized neonatal rat atrial myocytes (NRAMs), which allows toggling between proliferative and differentiated (ie, excitable and co... Abstract
Cited 11 times since 2022 (4.8 per year) source: EuropePMC
Nature biomedical engineering, Volume 6, Issue 4, 6 1 2022, Pages 389-402 Conditional immortalization of human atrial myocytes for the generation of in vitro models of atrial fibrillation. Harlaar N, Dekker SO, Zhang J, Snabel RR, Veldkamp MW, Verkerk AO, Fabres CC, Schwach V, Lerink LJS, Rivaud MR, Mulder AA, Corver WE, Goumans MJTH, Dobrev D, Klautz RJM, Schalij MJ, Veenstra GJC, Passier R, van Brakel TJ, Pijnappels DA, de Vries AAF
The lack of a scalable and robust source of well-differentiated human atrial myocytes constrains the development of in vitro models of atrial fibrillation (AF). Here we show that fully functional atrial myocytes can be generated and expanded one-quadrillion-fold via a conditional cell-immortalization method relying on lentiviral vectors and the doxycycline-controlled expression of a recombinant viral oncogene in human foetal atrial myocytes, and that the immortalized cells can be used to generat... Abstract
Cited 2 times since 2021 (0.7 per year) source: EuropePMC
Frontiers in physiology, Volume 12, 23 4 2021, Pages 710020 The Effects of Repetitive Use and Pathological Remodeling on Channelrhodopsin Function in Cardiomyocytes. Ördög B, Teplenin A, De Coster T, Bart CI, Dekker SO, Zhang J, Ypey DL, de Vries AAF, Pijnappels DA
Aim: Channelrhodopsins (ChRs) are a large family of light-gated ion channels with distinct properties, which is of great importance in the selection of a ChR variant for a given application. However, data to guide such selection for cardiac optogenetic applications are lacking. Therefore, we investigated the functioning of different ChR variants in normal and pathological hypertrophic cardiomyocytes subjected to various illumination protocols. Methods and Results: Isolated neonatal rat ventricul... Abstract
Cited 5 times since 2020 (1.3 per year) source: EuropePMC
eLife, Volume 9, 8 2 2020, Pages e55921 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
Cited 15 times since 2020 (3.7 per year) source: EuropePMC
Frontiers in cardiovascular medicine, Volume 7, 31 5 2020, Pages 43 Multicellular <i>In vitro</i> 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
Cited 2 times since 2020 (0.5 per year) source: EuropePMC
Journal of applied physiology (Bethesda, Md. : 1985), Volume 128, Issue 3, 30 5 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 24 times since 2019 (4.6 per year) source: EuropePMC
Science translational medicine, Volume 11, Issue 481, 1 1 2019, Pages eaau6447 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 15 times since 2018 (2.8 per year) source: EuropePMC
Cardiovascular research, Volume 114, Issue 14, 1 1 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 allo... Abstract
Cited 25 times since 2018 (4.5 per year) source: EuropePMC
eLife, Volume 7, 27 4 2018, Pages e41076 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 9 times since 2018 (1.5 per year) source: EuropePMC
Journal of cellular biochemistry, Volume 119, Issue 7, 10 2 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, 1 1 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
Cited 28 times since 2017 (4.3 per year) source: EuropePMC
Circulation. Arrhythmia and electrophysiology, Volume 10, Issue 11, 1 1 2017, Pages e005591 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 res... Abstract
Cited 58 times since 2017 (8.5 per year) source: EuropePMC
European heart journal, Volume 38, Issue 27, 1 1 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
Aims: 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 i... Abstract
Cited 20 times since 2017 (2.8 per year) source: EuropePMC
Cardiovascular research, Volume 113, Issue 3, 1 1 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 therefor... Abstract
Cited 59 times since 2016 (8 per year) source: EuropePMC
EMBO molecular medicine, Volume 8, Issue 12, 1 1 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