Journal article
Transforming Growth Factor Beta3 is Required for Cardiovascular Development
Journal of cardiovascular development and disease, v 7(2), p19
01 Jun 2020
PMID: 32456345
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Transforming growth factor beta3 (TGFB3) gene mutations in patients of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD1) and Loeys-Dietz syndrome-5 (LDS5)/Rienhoff syndrome are associated with cardiomyopathy, cardiac arrhythmia, cardiac fibrosis, cleft palate, aortic aneurysms, and valvular heart disease. Although the developing heart of embryos express Tgfb3, its overarching role remains unclear in cardiovascular development and disease. We used histological, immunohistochemical, and molecular analyses of Tgfb3(-/-) fetuses and compared them to wildtype littermate controls. The cardiovascular phenotypes were diverse with approximately two thirds of the Tgfb3(-/-) fetuses having one or more cardiovascular malformations, including abnormal ventricular myocardium (particularly of the right ventricle), outflow tract septal and alignment defects, abnormal aortic and pulmonary trunk walls, and thickening of semilunar and/or atrioventricular valves. Ventricular septal defects (VSD) including the perimembranous VSDs were observed in Tgfb3(-/-) fetuses with myocardial defects often accompanied by the muscular type VSD. In vitro studies using TGF beta 3-deficient fibroblasts in 3-D collagen lattice formation assays indicated that TGF beta 3 was required for collagen matrix reorganization. Biochemical studies indicated the 'paradoxically' increased activation of canonical (SMAD-dependent) and noncanonical (MAP kinase-dependent) pathways. TGF beta 3 is required for cardiovascular development to maintain a balance of canonical and noncanonical TGF beta signaling pathways.
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Details
- Title
- Transforming Growth Factor Beta3 is Required for Cardiovascular Development
- Creators
- Mrinmay Chakrabarti - University of South CarolinaNadia Al-Sammarraie - University of South CarolinaMengistu G. Gebere - University of South CarolinaAniket Bhattacharya - University of South CarolinaSunita Chopra - University of South CarolinaJohn Johnson - University of South CarolinaEdsel A. Pena - University of South CarolinaJohn F. Eberth - University of South CarolinaRobert E. Poelmann - Leiden University Medical CenterAdriana C. Gittenberger-de Groot - Leiden UniversityMohamad Azhar - University of South Carolina
- Publication Details
- Journal of cardiovascular development and disease, v 7(2), p19
- Publisher
- Mdpi
- Number of pages
- 21
- Grant note
- University of South Carolina R01HL126705; R01HL145064; R01CA218578-1A1 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 17GRNT33650018; 18PRE34080051 / American Heart Association University of South Carolina-ASPIRE I Postdoctoral Award
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000551261600012
- Scopus ID
- 2-s2.0-85096219858
- Other Identifier
- 991021902499204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems