PLN cardiomyopathy

Investigating and treating phospholamban cardiomyopathy

PLN cardiomyopathy

Phospholamban (PLN) plays a key role in calcium handling in heart muscle cells and as such impacts on proper contraction and relaxation of the heart.

Carriers of the PLN p.Arg14del pathogenic variant have a high risk of developing dilated cardiomyopathy (DCM) and/or arrhythmogenic cardiomyopathy (ACM) that may develop into heart failure.  A founder mutation of this pathogenic variant was described by us and ±14% of Dutch DCM and ACM patients carry this pathogenic variant. Meanwhile, this pathogenic variant has also been found in other European countries, USA, Canada and in China, suggesting that it may be more widespread than originally anticipated. There is no established treatment for these patients other than standard heart failure therapy or heart transplantation.

We are the main PLN cardiomyopathy centrum in the Netherlands and together with our collaborators we investigate this syndrome at multiple levels in order to find therapeutic options to fight this disease. Amongst others, we participate in clinical PLN-R14del carrier registry, investigate clinical therapies (iPhorecast study) and investigate genetic and molecular aspects of this disease. The latter is performed in our own laboratory using state of the art techniques, including induced pluripotent stem cell (iPSC) technology, transgenic animal models and bioinformatics.

We are looking for enthusiastic PhD students and post-docs, both medical doctors and biologists to investigate the pathology of PLN cardiomyopathy and to test tailor made therapies targeting this disease.

National and international collaborations

Prof. Jolanda van der Velde, Amsterdam, The Netherlands
Prof. Pieter Doevedans, Utrecht, The Netherlands
Prof. P. van Van Tintelen, Utrecht, The Netherlands
Prof. F. Asselbergs, Utrecht, The Netherlands
Prof. A.M. de Wilde, Amsterdam, The Netherlands
Dr. B. Boukens, Amsterdam, The Netherlands
Prof. Litza Kranias, Cincinnati, USA
Prof. Stefan Lehnart, Göttingen, Germany
Prof. M. Mercola, Stanford, USA
Prof. Kevin Costa, New York, USA



Principal investigators

Joris van den Hurk

PhD Student

Belend Mahmoud


Peter van der Meer


Herman Silljé


Daan Westenbrink


Niels Grote Beverborg


Vivian Oliveira Nunes Teixeira


Frits Deiman

PhD Student

Remco de Brouwer


Nienke Stege

Persberichten en publicaties

Distinct molecular signature of phospholamban p.Arg14del arrhythmogenic cardiomyopathy

Te Rijdt WP, Asimaki A, Jongbloed JDH, Hoorntje ET, Lazzarini E, van der Zwaag PA, de Boer RA, van Tintelen JP, Saffitz JE, van den Berg MP, Suurmeijer AJH. Cardiovasc Pathol. 2019.

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Myocardial fibrosis as an early feature in phospholamban p.Arg14del mutation carriers: phenotypic insights from cardiovascular magnetic resonance imaging.

Te Rijdt WP, Ten Sande JN, Gorter TM, van der Zwaag PA, van Rijsingen IA, Boekholdt SM, van Tintelen JP, van Haelst PL, Planken RN, de Boer RA, Suurmeijer AJH, van Veldhuisen DJ, Wilde AAM, Willems TP, van Dessel PFHM, van den Berg MP. Eur Heart J Cardiovasc Imaging. 2019

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Phospholamban R14del in patients with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. Evidence supporting the concept for arrhythmogenic cardiomyopathy.

van der Zwaag PA, van Rijsingen IAW, Asimaki A, Jongbloed JDH, van Veldhuisen DJ, Wiesfeld ACP, Cox MGPJ, van Lochem LT, de Boer RA, Christiaans I, Ronald H. Lekanne dit Deprez RH, Judge DP,Calkins H, Suurmeijer AJH, Hauer RNW, Saffitz JE, Wilde AAM, van den Berg MP, van Tintelen JP. Eur J Heart Fail 2012

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Phospholamban immunostaining is a highly sensitive and specific method for diagnosing phospholamban p.Arg14del cardiomyopathy.

Te Rijdt WP, van der Klooster ZJ, Hoorntje ET, Jongbloed JDH, van der Zwaag PA, Asselbergs FW, Dooijes D, de Boer RA, van Tintelen JP, van den Berg MP, Vink A, Suurmeijer AJH. Cardiovasc Pathol. 2017

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Arrhythmogenic right ventricular dysplasia/cardiomyopathy according to revised 2010 task force criteria with inclusion of non-desmosomal phospholamban mutation carriers.

Groeneweg JA, van der Zwaag PA, Olde Nordkamp LR, Bikker H, Jongbloed JD, Jongbloed R, Wiesfeld AC, Cox MG, van der Heijden JF, Atsma DE, de Boer K, Doevendans PA, Vink A, van Veen TA, Dooijes D, van den Berg MP, Wilde AA, van Tintelen JP, Hauer RN. Am J Cardiol. 2013

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