title: Perturbations of mechanotransduction and aneurysm formation in heritable aortopathies.
abstract: Thoracic aortic aneurysm and dissection in young and middle aged patients is increasingly recognised as due to genetic aortopathy. Mutations in multiple genes affecting proteins in the extracellular matrix, microfibrillar structure, the endothelium and cell signalling pathways have been associated with thoracic aortic disease. The TGFß signalling pathway appears to play a key role in mediating abnormal aortic growth and aneurysm formation. A challenge remains in understanding how the many different gene mutations can result in deranged TGFß signalling. This review examines the functional relationships between key structural and signalling proteins, with reference to the need for maintenance of homeostasis in mechanotransduction within the aortic wall. A mechanism, through which perturbations in mechanotransduction, arising from different gene mutations, results in altered TGFß signalling is described.
authors.affiliation: Sydney Medical School, University of Sydney, NSW, Australia. Electronic address: richmond.jeremy@sydney.edu.au.
authors.forename: Richmond W
authors.initials: RW
authors.lastname: Jeremy
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Robertson
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Lu
authors.forename: Brett D
authors.initials: BD
authors.lastname: Hambly
mesh_terms: D000784:Aortic Dissection / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D016212:Transforming Growth Factor beta
keywords: Aneurysm; Aorta; Gene; Mechanotransduction; Mutation