The Role of the TGF-β Superfamily in Myocardial Infarction
The members of the transforming growth factor β (TGF-β) superfamily are essential regulators of cell differentiation, phenotype and function, and have been implicated in the pathogenesis of many diseases. Myocardial infarction is associated with induction of several members of the superfamily, inclu...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcvm.2019.00140/full |
| _version_ | 1818985710188756992 |
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| author | Anis Hanna Nikolaos G. Frangogiannis |
| author_facet | Anis Hanna Nikolaos G. Frangogiannis |
| author_sort | Anis Hanna |
| collection | DOAJ |
| description | The members of the transforming growth factor β (TGF-β) superfamily are essential regulators of cell differentiation, phenotype and function, and have been implicated in the pathogenesis of many diseases. Myocardial infarction is associated with induction of several members of the superfamily, including TGF-β1, TGF-β2, TGF-β3, bone morphogenetic protein (BMP)-2, BMP-4, BMP-10, growth differentiation factor (GDF)-8, GDF-11 and activin A. This manuscript reviews our current knowledge on the patterns and mechanisms of regulation and activation of TGF-β superfamily members in the infarcted heart, and discusses their cellular actions and downstream signaling mechanisms. In the infarcted heart, TGF-β isoforms modulate cardiomyocyte survival and hypertrophic responses, critically regulate immune cell function, activate fibroblasts, and stimulate a matrix-preserving program. BMP subfamily members have been suggested to exert both pro- and anti-inflammatory actions and may regulate fibrosis. Members of the GDF subfamily may also modulate survival and hypertrophy of cardiomyocytes and regulate inflammation. Important actions of TGF-β superfamily members may be mediated through activation of Smad-dependent or non-Smad pathways. The critical role of TGF-β signaling cascades in cardiac repair, remodeling, fibrosis, and regeneration may suggest attractive therapeutic targets for myocardial infarction patients. However, the pleiotropic, cell-specific, and context-dependent actions of TGF-β superfamily members pose major challenges in therapeutic translation. |
| first_indexed | 2024-12-20T18:39:13Z |
| format | Article |
| id | doaj.art-d0252e681f9846e7aef8ed6678c294ad |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-20T18:39:13Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-d0252e681f9846e7aef8ed6678c294ad2022-12-21T19:29:52ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2019-09-01610.3389/fcvm.2019.00140478333The Role of the TGF-β Superfamily in Myocardial InfarctionAnis HannaNikolaos G. FrangogiannisThe members of the transforming growth factor β (TGF-β) superfamily are essential regulators of cell differentiation, phenotype and function, and have been implicated in the pathogenesis of many diseases. Myocardial infarction is associated with induction of several members of the superfamily, including TGF-β1, TGF-β2, TGF-β3, bone morphogenetic protein (BMP)-2, BMP-4, BMP-10, growth differentiation factor (GDF)-8, GDF-11 and activin A. This manuscript reviews our current knowledge on the patterns and mechanisms of regulation and activation of TGF-β superfamily members in the infarcted heart, and discusses their cellular actions and downstream signaling mechanisms. In the infarcted heart, TGF-β isoforms modulate cardiomyocyte survival and hypertrophic responses, critically regulate immune cell function, activate fibroblasts, and stimulate a matrix-preserving program. BMP subfamily members have been suggested to exert both pro- and anti-inflammatory actions and may regulate fibrosis. Members of the GDF subfamily may also modulate survival and hypertrophy of cardiomyocytes and regulate inflammation. Important actions of TGF-β superfamily members may be mediated through activation of Smad-dependent or non-Smad pathways. The critical role of TGF-β signaling cascades in cardiac repair, remodeling, fibrosis, and regeneration may suggest attractive therapeutic targets for myocardial infarction patients. However, the pleiotropic, cell-specific, and context-dependent actions of TGF-β superfamily members pose major challenges in therapeutic translation.https://www.frontiersin.org/article/10.3389/fcvm.2019.00140/fullTGF-βmyocardial infarctionSmadBMPGDFfibrosis |
| spellingShingle | Anis Hanna Nikolaos G. Frangogiannis The Role of the TGF-β Superfamily in Myocardial Infarction Frontiers in Cardiovascular Medicine TGF-β myocardial infarction Smad BMP GDF fibrosis |
| title | The Role of the TGF-β Superfamily in Myocardial Infarction |
| title_full | The Role of the TGF-β Superfamily in Myocardial Infarction |
| title_fullStr | The Role of the TGF-β Superfamily in Myocardial Infarction |
| title_full_unstemmed | The Role of the TGF-β Superfamily in Myocardial Infarction |
| title_short | The Role of the TGF-β Superfamily in Myocardial Infarction |
| title_sort | role of the tgf β superfamily in myocardial infarction |
| topic | TGF-β myocardial infarction Smad BMP GDF fibrosis |
| url | https://www.frontiersin.org/article/10.3389/fcvm.2019.00140/full |
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