TGF-β Signaling in Control of Cardiovascular Function
Marie-José Goumans1, Peter Ten Dijke1
1Department of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Insights
Transforming growth factor β (TGF-β) signaling is crucial for vascular health. Its disruption causes hereditary and nonhereditary vascular diseases, impacting cell behavior and contributing to cardiovascular conditions.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Cell Biology
Background:
- Gene mutations affecting transforming growth factor β (TGF-β) signaling are linked to hereditary vascular syndromes like Osler-Rendu-Weber disease and Marfan syndrome.
- Dysregulated TGF-β signaling also contributes to nonhereditary conditions such as atherosclerosis and cardiac fibrosis.
Purpose of the Study:
- To review the multifaceted roles of TGF-β in vascular development and disease.
- To highlight the significance of TGF-β signaling in vasculogenesis, angiogenesis, and lymphangiogenesis.
- To discuss the implications of TGF-β pathway deregulation in cardiovascular pathologies.
Main Methods:
- Review of genetic studies in animals and humans.
- Analysis of cell culture data from endothelial cells and smooth muscle cells (SMCs).
- Examination of TGF-β's effects on cellular processes in various culture models.
Main Results:
- TGF-β critically influences endothelial and SMC proliferation, differentiation, migration, tube formation, and sprouting.
- TGF-β promotes endothelial-to-mesenchymal transition, vital for heart development and vascular pathology.
- Deregulation of TGF-β signaling is implicated in a spectrum of cardiovascular diseases.
Conclusions:
- TGF-β signaling is a central regulator of vascular development and homeostasis.
- Aberrant TGF-β signaling underlies numerous vascular disorders, from hereditary syndromes to acquired diseases.
- Understanding TGF-β's role is key to developing therapeutic strategies for cardiovascular diseases.
Abstract:
Genetic studies in animals and humans indicate that gene mutations that functionally perturb transforming growth factor β (TGF-β) signaling are linked to specific hereditary vascular syndromes, including Osler-Rendu-Weber disease or hereditary hemorrhagic telangiectasia and Marfan syndrome. Disturbed TGF-β signaling can also cause nonhereditary disorders like atherosclerosis and cardiac fibrosis. Accordingly, cell culture studies using endothelial cells or smooth muscle cells (SMCs), cultured alone or together in two- or three-dimensional cell culture assays, on plastic or embedded in matrix, have shown that TGF-β has a pivotal effect on endothelial and SMC proliferation, differentiation, migration, tube formation, and sprouting. Moreover, TGF-β can stimulate endothelial-to-mesenchymal transition, a process shown to be of key importance in heart valve cushion formation and in various pathological vascular processes. Here, we discuss the roles of TGF-β in vasculogenesis, angiogenesis, and lymphangiogenesis and the deregulation of TGF-β signaling in cardiovascular diseases.
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