Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model

Autor:	Sahar Isa Da’as, Waseem Hasan, Rola Salem, Nadine Younes, Doua Abdelrahman, Iman A. Mohamed, Arwa Aldaalis, Ramzi Temanni, Lisa Sara Mathew, Stephan Lorenz, Magdi Yacoub, Michail Nomikos, Gheyath K. Nasrallah, Khalid A. Fakhro
Jazyk:	angličtina
Rok vydání:	2022
Předmět:	Hyperplasia Organic Chemistry General Medicine Cardiomyopathy Hypertrophic Actins Catalysis Computer Science Applications Inorganic Chemistry hypertrophic cardiomyopathy HCM c-MYBPC3 actin RNA seq zebrafish knockout Mutation Animals Myocytes Cardiac Physical and Theoretical Chemistry Carrier Proteins Transcriptome Cardiac Myosins Molecular Biology Zebrafish Spectroscopy
Zdroj:	International Journal of Molecular Sciences; Volume 23; Issue 16; Pages: 8840
ISSN:	1422-0067
DOI:	10.3390/ijms23168840
Popis:	Variants 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52f8469169f445c5aac84e954b5e6548 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.