Article ; Online: TGF-β as a therapeutic target in the infarcted and failing heart: cellular mechanisms, challenges, and opportunities.
Expert opinion on therapeutic targets
2024 Volume 28, Issue 1-2, Page(s) 45–56
Abstract: Introduction: Myocardial fibrosis accompanies most cardiac conditions and can be reparative or maladaptive. Transforming Growth Factor (TGF)-β is a potent fibrogenic mediator, involved in repair, remodeling, and fibrosis of the injured heart.: Areas ... ...
Abstract | Introduction: Myocardial fibrosis accompanies most cardiac conditions and can be reparative or maladaptive. Transforming Growth Factor (TGF)-β is a potent fibrogenic mediator, involved in repair, remodeling, and fibrosis of the injured heart. Areas covered: This review manuscript discusses the role of TGF-β in heart failure focusing on cellular mechanisms and therapeutic implications. TGF-β is activated in infarcted, remodeling and failing hearts. In addition to its fibrogenic actions, TGF-β has a broad range of effects on cardiomyocytes, immune, and vascular cells that may have both protective and detrimental consequences. TGF-β-mediated effects on macrophages promote anti-inflammatory transition, whereas actions on fibroblasts mediate reparative scar formation and effects on pericytes are involved in maturation of infarct neovessels. On the other hand, TGF-β actions on cardiomyocytes promote adverse remodeling, and prolonged activation of TGF-β signaling in fibroblasts stimulates progression of fibrosis and heart failure. Expert opinion: Understanding of the cell-specific actions of TGF-β is necessary to design therapeutic strategies in patients with myocardial disease. Moreover, to implement therapeutic interventions in the heterogeneous population of heart failure patients, mechanism-driven classification of both HFrEF and HFpEF patients is needed. Heart failure patients with prolonged or overactive fibrogenic TGF-β responses may benefit from cautious TGF-β inhibition. |
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MeSH term(s) | Humans ; Heart Failure/drug therapy ; Transforming Growth Factor beta/metabolism ; Stroke Volume ; Myocardial Infarction/therapy ; Fibroblasts/metabolism ; Fibrosis ; Myocardium/pathology |
Chemical Substances | Transforming Growth Factor beta |
Language | English |
Publishing date | 2024-02-19 |
Publishing country | England |
Document type | Journal Article ; Review |
ZDB-ID | 2055208-7 |
ISSN | 1744-7631 ; 1472-8222 |
ISSN (online) | 1744-7631 |
ISSN | 1472-8222 |
DOI | 10.1080/14728222.2024.2316735 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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