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Open AccessArticle

Myocardial TGFβ2 Is Required for Atrioventricular Cushion Remodeling and Myocardial Development

1
Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA
2
William Jennings Bryan Dorn VA Medical Center, Dorn Research Institute, Columbia, SC 29209, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Andy Wessels
J. Cardiovasc. Dev. Dis. 2021, 8(3), 26; https://doi.org/10.3390/jcdd8030026
Received: 24 January 2021 / Revised: 18 February 2021 / Accepted: 26 February 2021 / Published: 2 March 2021
(This article belongs to the Special Issue Mitral Valve Development and Disease)
Among the three transforming growth factor beta (TGFβ) ligands, TGFβ2 is essential for heart development and is produced by multiple cell types, including myocardium. Heterozygous mutations in TGFB2 in patients of connective tissue disorders result in congenital heart defects and adult valve malformations, including mitral valve prolapse (MVP) with or without regurgitation. Tgfb2 germline knockout fetuses exhibit multiple cardiac defects but the role of myocardial-TGFβ2 in heart development is yet to be elucidated. Here, myocardial Tgfb2 conditional knockout (CKO) embryos were generated by crossing Tgfb2flox mice with Tgfb2+/−; cTntCre mice. Tgfb2flox/− embryos were normal, viable. Cell fate mapping was done using dual-fluorescent mT/mG+/− mice. Cre-mediated Tgfb2 deletion was assessed by genomic PCR. RNAscope in situ hybridization was used to detect the loss of myocardial Tgfb2 expression. Histological, morphometric, immunohistochemical, and in situ hybridization analyses of CKOs and littermate controls at different stages of heart development (E12.5–E18.5) were used to determine the role of myocardium-derived TGFβ2 in atrioventricular (AV) cushion remodeling and myocardial development. CKOs exhibit a thin ventricular myocardium, AV cushion remodeling defects and developed incomplete AV septation defects. The loss of myocardial Tgfb2 resulted in impaired cushion maturation and dysregulated cell death. Phosphorylated SMAD2, a surrogate for TGFβ signaling, was “paradoxically” increased in both AV cushion mesenchyme and ventricular myocardium in the CKOs. Our results indicate that TGFβ2 produced by cardiomyocytes acting as cells autonomously on myocardium and via paracrine signaling on AV cushions are required for heart development. View Full-Text
Keywords: TGFβ2; myocardium; atrioventricular cushion; AVSD; mitral valve; SMAD2 TGFβ2; myocardium; atrioventricular cushion; AVSD; mitral valve; SMAD2
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MDPI and ACS Style

Bhattacharya, A.; Al-Sammarraie, N.; Gebere, M.G.; Johnson, J.; Eberth, J.F.; Azhar, M. Myocardial TGFβ2 Is Required for Atrioventricular Cushion Remodeling and Myocardial Development. J. Cardiovasc. Dev. Dis. 2021, 8, 26. https://doi.org/10.3390/jcdd8030026

AMA Style

Bhattacharya A, Al-Sammarraie N, Gebere MG, Johnson J, Eberth JF, Azhar M. Myocardial TGFβ2 Is Required for Atrioventricular Cushion Remodeling and Myocardial Development. Journal of Cardiovascular Development and Disease. 2021; 8(3):26. https://doi.org/10.3390/jcdd8030026

Chicago/Turabian Style

Bhattacharya, Aniket; Al-Sammarraie, Nadia; Gebere, Mengistu G.; Johnson, John; Eberth, John F.; Azhar, Mohamad. 2021. "Myocardial TGFβ2 Is Required for Atrioventricular Cushion Remodeling and Myocardial Development" J. Cardiovasc. Dev. Dis. 8, no. 3: 26. https://doi.org/10.3390/jcdd8030026

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