title: Pathophysiology of thoracic aortic aneurysm (TAA): is it not one uniform aorta? Role of embryologic origin.
abstract: Thoracic aortic aneurysm (TAA) is a clinically silent and potentially fatal disease whose pathophysiology is poorly understood. Application of data derived from animal models and human tissue analysis of abdominal aortic aneurysms may prove misleading given current evidence of structural and biochemical aortic heterogeneity above and below the diaphragm. Genetic predisposition is more common in TAA and includes multi-faceted syndromes such as Marfan, Loeys-Dietz, and type IV Ehlers-Danlos as well as autosomal-dominant familial patterns of inheritance. Investigation into the consequences of these known mutations has provided insight into the cell signaling cascades leading to degenerative remodeling of the aortic medial extracellular matrix (ECM) with TGF-β playing a major role. Targeted research into modifying the upstream regulation or downstream effects of the TGF-β1 pathway may provide opportunities for intervention to attenuate TAA progression.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Medical University of South Carolina, Charlston, SC, USA.
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Ruddy
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Jones
authors.forename: John S
authors.initials: JS
authors.lastname: Ikonomidis
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000196:embryology / Q000378:metabolism / Q000503:physiopathology*; D017545:Aortic Aneurysm, Thoracic / Q000196:embryology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D020782:Matrix Metalloproteinases
keywords: AAA; AT1; AngII; ECM; ERK; Extracellular matrix remodeling; MMP; Matrix metalloproteinases; TAA; TGF-β; TGF-βR1 & 2; Thoracic Aortic Aneurysm; Transforming growth factor-beta; VSMC; abdominal aortic aneurysm; angiotensin II; angiotensin receptor 1; extracellular matrix; extracellular signal-regulated kinase; matrix metalloproteinase; t-PA; thoracic aortic aneurysm; tissue plasminogen activator; transforming growth factor beta; transforming growth factor beta receptor 1 & 2; vascular smooth muscle cell