Contractile Dysfunction Irrespective of the Mutant Protein in Human Hypertrophic Cardiomyopathy With Normal Systolic Function

Sabine Dijk, ER Paalberends, A (Aref) Najafi, Michelle Michels, S Sadayappan, L Carrier, NM Boontje, Diederik Kuster, M van Slegtenhorst, D Dooijes, C dos Remedios, Folkert ten Cate, GJM Stienen, J Velden

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Background-Hypertrophic cardiomyopathy (HCM), typically characterized by asymmetrical left ventricular hypertrophy, frequently is caused by mutations in sarcomeric proteins. We studied if changes in sarcomeric properties in HCM depend on the underlying protein mutation. Methods and Results-Comparisons were made between cardiac samples from patients carrying a MYBPC3 mutation (MYBPC3(mut); n = 17), mutation negative HCM patients without an identified sarcomere mutation (HCM(mn); n = 11), and nonfailing donors (n = 12). All patients had normal systolic function, but impaired diastolic function. Protein expression of myosin binding protein C (cMyBP-C) was significantly lower in MYBPC3(mut) by 33 +/- 5%, and similar in HCM(mn) compared with donor. cMyBP-C phosphory Conclusions-Changes in sarcomere function reflect the clinical HCM phenotype rather than the specific MYBPC3 mutation. Hypocontractile sarcomeres are a common deficit in human HCM with normal systolic left ventricular function and may contribute to HCM disease progression. (Circ Heart Fail. 2012; 5: 36-46.)
Original languageUndefined/Unknown
Pages (from-to)36-U126
JournalCirculation-Heart Failure
Issue number1
Publication statusPublished - 2012

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