Impact of the Transforming Growth Factor β (TGF-β) on Brain Aneurysm Formation and Development: A Literature Review

Abstract

The mechanisms underlying the formation and rupture of intracranial aneurysms remain unclear. Rupture of the aneurysmal wall causes subarachnoid hemorrhage, with a mortality rate of 35-50%. Literature suggests that rupture is associated with the remodeling of the aneurysmal wall, including endothelial cell damage, smooth muscle cells (SMCs) proliferation, and inflammatory cell infiltration, particularly macrophages. Transforming growth factor β (TGF-β) is a multifunctional factor that plays a diverse role in cell growth and differentiation. It is crucial for strengthening vessel walls during angiogenesis and also regulates the proliferation of SMCs, indicating the potential involvement of TGF-β signaling in the pathogenesis and development of cerebral aneurysms. This review examines the complex role of TGF-β, its receptors, and signaling pathways in cerebral aneurysm formation and progression. Understanding the molecular mechanisms of TGF-β signaling in aneurysm development is vital for identifying potential therapeutic targets to prevent aneurysm rupture. Further research is necessary to fully elucidate the role of TGF-β in aneurysm pathophysiology, which could lead to the development of novel therapeutic strategies for aneurysm prevention and management, particularly in preventing subarachnoid hemorrhage.

Keywords: Cerebral artery; Endothelial cells (ECs); Intracranial aneurysm; Macrophages; Smooth muscle cells (SMCs); Transforming growth factor β (TGF-β).

Fig. 1

The TGF-β family members. BMPs bone morphogenic proteins, GDFs growth differentiation factors, MIS/AMH Müllerian-inhibiting substance/anti-Müllerian hormone, TGF-β transforming growth factor β

Fig. 2

The pleiotropic effects of TGF-β on diverse cell populations. ECM extracellular matrix, ECs endothelial cells, EMT epithelial-mesenchymal transition, IgA immunoglobulin A, N1 neutrophils N1 type, N2 neutrophils N2 type, NK cells natural killer cells, SMCs smooth muscle cells, TGF-β transforming growth factor β

Fig. 3

A Structural features of the normal cerebral artery. B Structural features of the aneurysmal cerebral artery. CSF cerebrospinal fluid, ECs endothelial cells, ECM extracellular matrix, EEL external elastic membrane, IEL external elastic lamina, SMCs smooth muscle cells

Fig. 4

Impact of the transforming growth factor β (TGF-β) on brain aneurysm formation and development. HIF1A-AS1 hypoxia-inducible factor-1α—antisense RNA 1, HIF-1α hypoxia-inducible factor-1α, MAPK mitogen-activated protein kinase, miR microRNA, NOX4 NADPH, oxidase 4; RNA ribonucleic acid, SMAD3 SMAD3 gene, SMCs smooth muscle cells, SPARC secreted protein acidic and rich in cysteine, TGFB2 transforming growth factor beta 2 gene, TGFBR1 transforming growth factor beta receptor 1 gene, TGFBR2 transforming growth factor beta receptor 2 gene, TGF-β transforming growth factor β, TβR transforming growth factor beta receptor. All figures were created with BioRender.com