دورية أكاديمية
Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy
| العنوان: | Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy |
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| المؤلفون: | Schuldt, M. (Maike), Pei, J. (Jiayi), Harakalova, M. (Magdalena), Dorsch, L.M. (Larissa M.), Schlossarek, S. (Saskia), Mokry, M. (Michal), Knol, J.C. (Jaco), Pham, T.V. (Thang V.), Schelfhorst, T. (Tim), Piersma, S.R. (Sander R.), Dos Remedios, C. (Cris), Dalinghaus, M. (Michiel), Michels, M. (Michelle), Asselbergs, F.W. (Folkert W.), Moutin, M.-J. (Marie-Jo), Carrier, L. (Lucie), Jimenez, C.R. (Connie), Velden, J. (Jolanda) van der, Kuster, D.W.D. (Diederik) |
| المصدر: | Circulation. Heart Failure vol. 14 no. 1 |
| سنة النشر: | 2021 |
| المجموعة: | RePub - Publications from Erasmus University, Rotterdam |
| مصطلحات موضوعية: | cardiomyopathies, genotype, heart diseases, mutation, proteomics, treatment, tubulin |
| الوصف: | BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCMSMP), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCMSMN). Genotype-specific differences have been reported in cardiac function. Moreover, HCMSMN patients have later disease onset and a better prognosis than HCMSMP patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group. METHODS: A proteomics screen was performed in cardiac tissue from 39 HCMSMP patients, 11HCMSMN patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel MYBPC32373insG mouse model was used to confirm functional relevance of our proteomic findings. RESULTS: In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of to |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | http://repub.eur.nl/pub/134435Test; urn:hdl:1765/134435 |
| DOI: | 10.1161/CIRCHEARTFAILURE.120.007022 |
| الإتاحة: | https://doi.org/10.1161/CIRCHEARTFAILURE.120.007022Test http://repub.eur.nl/pub/134435Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.CCE74912 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1161/CIRCHEARTFAILURE.120.007022 |
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