Mutation-specific pathology and treatment of hypertrophic cardiomyopathy in patients, mouse models and human engineered heart tissue

Paul J.M. Wijnker*, Jolanda van der Velden

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review


Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and is characterized by asymmetric left ventricular hypertrophy and diastolic dysfunction, and a frequent cause of sudden cardiac death at young age. Pharmacological treatment to prevent or reverse HCM is lacking. This may be partly explained by the variety of underlying disease causes. Over 1500 mutations have been associated with HCM, of which the majority reside in genes encoding sarcomere proteins, the cardiac contractile building blocks. Several mutation-mediated disease mechanisms have been identified, with proof for gene- and mutation-specific cellular perturbations. In line with mutation-specific changes in cellular pathology, the response to treatment may depend on the underlying sarcomere gene mutation. In this review, we will discuss evidence for mutation-specific pathology and treatment responses in HCM patients, mouse models and engineered heart tissue. The pros and cons of these experimental models for studying mutation-specific HCM pathology and therapies will be outlined.

Original languageEnglish
Article number165774
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number8
Publication statusPublished - 1 Aug 2020

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