Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model
<div><p>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 generate...
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| مؤلفون آخرون: | , , , , , , , , , , , , |
| منشور في: |
2022
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| _version_ | 1864513519642214400 |
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| author | Sahar Isa Da’as (18288880) |
| author2 | Waseem Hasan (17280670) Rola Salem (18288883) Nadine Younes (14779150) Doua Abdelrahman (17280667) Iman A. Mohamed (18288886) Arwa Aldaalis (13355328) Ramzi Temanni (671528) Lisa Sara Mathew (17886698) Stephan Lorenz (466378) Magdi Yacoub (6893000) Michail Nomikos (17563188) Gheyath K. Nasrallah (9200525) Khalid A. Fakhro (3158862) |
| author2_role | author author author author author author author author author author author author author |
| author_facet | Sahar Isa Da’as (18288880) Waseem Hasan (17280670) Rola Salem (18288883) Nadine Younes (14779150) Doua Abdelrahman (17280667) Iman A. Mohamed (18288886) Arwa Aldaalis (13355328) Ramzi Temanni (671528) Lisa Sara Mathew (17886698) Stephan Lorenz (466378) Magdi Yacoub (6893000) Michail Nomikos (17563188) Gheyath K. Nasrallah (9200525) Khalid A. Fakhro (3158862) |
| author_role | author |
| dc.creator.none.fl_str_mv | Sahar Isa Da’as (18288880) Waseem Hasan (17280670) Rola Salem (18288883) Nadine Younes (14779150) Doua Abdelrahman (17280667) Iman A. Mohamed (18288886) Arwa Aldaalis (13355328) Ramzi Temanni (671528) Lisa Sara Mathew (17886698) Stephan Lorenz (466378) Magdi Yacoub (6893000) Michail Nomikos (17563188) Gheyath K. Nasrallah (9200525) Khalid A. Fakhro (3158862) |
| dc.date.none.fl_str_mv | 2022-08-09T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/ijms23168840 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Transcriptome_Profile_Identifies_Actin_as_an_Essential_Regulator_of_Cardiac_Myosin_Binding_Protein_C3_Hypertrophic_Cardiomyopathy_in_a_Zebrafish_Model/25524007 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Zoology Chemical sciences Inorganic chemistry Organic chemistry Physical chemistry Theoretical and computational chemistry hypertrophic cardiomyopathy HCM c-MYBPC3 actin RNA seq zebrafish knockout |
| dc.title.none.fl_str_mv | Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <div><p>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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: International Journal of Molecular Sciences<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms23168840" target="_blank">https://dx.doi.org/10.3390/ijms23168840</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_46c4a3d772347ee19d21531ad023804e |
| identifier_str_mv | 10.3390/ijms23168840 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25524007 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish ModelSahar Isa Da’as (18288880)Waseem Hasan (17280670)Rola Salem (18288883)Nadine Younes (14779150)Doua Abdelrahman (17280667)Iman A. Mohamed (18288886)Arwa Aldaalis (13355328)Ramzi Temanni (671528)Lisa Sara Mathew (17886698)Stephan Lorenz (466378)Magdi Yacoub (6893000)Michail Nomikos (17563188)Gheyath K. Nasrallah (9200525)Khalid A. Fakhro (3158862)Biological sciencesZoologyChemical sciencesInorganic chemistryOrganic chemistryPhysical chemistryTheoretical and computational chemistryhypertrophic cardiomyopathyHCMc-MYBPC3actinRNA seqzebrafish knockout<div><p>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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: International Journal of Molecular Sciences<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms23168840" target="_blank">https://dx.doi.org/10.3390/ijms23168840</a></p>2022-08-09T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ijms23168840https://figshare.com/articles/journal_contribution/Transcriptome_Profile_Identifies_Actin_as_an_Essential_Regulator_of_Cardiac_Myosin_Binding_Protein_C3_Hypertrophic_Cardiomyopathy_in_a_Zebrafish_Model/25524007CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/255240072022-08-09T03:00:00Z |
| spellingShingle | Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model Sahar Isa Da’as (18288880) Biological sciences Zoology Chemical sciences Inorganic chemistry Organic chemistry Physical chemistry Theoretical and computational chemistry hypertrophic cardiomyopathy HCM c-MYBPC3 actin RNA seq zebrafish knockout |
| status_str | publishedVersion |
| title | Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model |
| title_full | Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model |
| title_fullStr | Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model |
| title_full_unstemmed | Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model |
| title_short | Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model |
| title_sort | Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model |
| topic | Biological sciences Zoology Chemical sciences Inorganic chemistry Organic chemistry Physical chemistry Theoretical and computational chemistry hypertrophic cardiomyopathy HCM c-MYBPC3 actin RNA seq zebrafish knockout |