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AuthorDa’as, Sahar Isa
AuthorHasan, Waseem
AuthorSalem, Rola
AuthorYounes, Nadine
AuthorAbdelrahman, Doua
AuthorMohamed, Iman A.
AuthorAldaalis, Arwa
AuthorTemanni, Ramzi
AuthorMathew, Lisa Sara
AuthorLorenz, Stephan
AuthorYacoub, Magdi
AuthorNomikos, Michail
AuthorNasrallah, Gheyath K.
AuthorFakhro, Khalid A.
Available date2023-09-28T05:03:08Z
Publication Date2022-08-01
Publication NameInternational Journal of Molecular Sciences
Identifierhttp://dx.doi.org/10.3390/ijms23168840
CitationDa’as, S.I.; Hasan, W.; Salem, R.; Younes, N.; Abdelrahman, D.; Mohamed, I.A.; Aldaalis, A.; Temanni, R.; Mathew, L.S.; Lorenz, S.; et al. Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model. Int. J. Mol. Sci. 2022, 23, 8840. https://doi.org/10.3390/ijms23168840
ISSN16616596
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85136555150&origin=inward
URIhttp://hdl.handle.net/10576/48012
AbstractVariants in cardiac myosin-binding protein C (cMyBP-C) are the leading cause of inherited hypertrophic cardiomyopathy (HCM), demonstrating the key role that cMyBP-C plays in the heart’s contractile machinery. To investigate the c-MYBPC3 HCM-related cardiac impairment, we generated a zebrafish mypbc3-knockout model. These knockout zebrafish displayed significant morphological heart alterations related to a significant decrease in ventricular and atrial diameters at systolic and diastolic states at the larval stages. Immunofluorescence staining revealed significant hyperplasia in the mutant’s total cardiac and ventricular cardiomyocytes. Although cardiac contractility was similar to the wild-type control, the ejection fraction was significantly increased in the mypbc3 mutants. At later stages of larval development, the mutants demonstrated an early cardiac phenotype of myocardium remodeling, concurrent cardiomyocyte hyperplasia, and increased ejection fraction as critical processes in HCM initiation to counteract the increased ventricular myocardial wall stress. The examination of zebrafish adults showed a thickened ventricular cardiac wall with reduced heart rate, swimming speed, and endurance ability in both the mypbc3 heterozygous and homozygous groups. Furthermore, heart transcriptome profiling showed a significant downregulation of the actin-filament-based process, indicating an impaired actin cytoskeleton organization as the main dysregulating factor associated with the early ventricular cardiac hypertrophy in the zebrafish mypbc3 HCM model.
SponsorThis research was supported by the Qatar Foundation, Qatar Cardiovascular Research Center and was funded by the Sidra Medicine, Research and Development Fund of the Zebrafish Functional Genomics Core Facility. Institutional Review Board Statement The animal study protocol was approved by the Institutional Review Board (or Ethics Committee) of Qatar University (QU-IACUC 2-9/2019-1).
Languageen
PublisherMDPI
Subjectactin
c-MYBPC3
HCM
hypertrophic cardiomyopathy
RNA seq
zebrafish knockout
TitleTranscriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model
TypeArticle
Issue Number16
Volume Number23
ESSN1422-0067
dc.accessType Open Access


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