Pathophysiology of Thoracic Aortic Aneurysm (TAA): Is It Not One Uniform Aorta? Role of Embryologic Origin

• Published in: Progress in cardiovascular diseases Vol. 56; no. 1; pp. 68 - 73
• Main Authors: Ruddy, Jean Marie, Jones, Jeffery A, Ikonomidis, John S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2013
• Subjects: Animals; Aorta, Thoracic - embryology; Aorta, Thoracic - metabolism; Aorta, Thoracic - physiopathology; Aortic Aneurysm, Thoracic - embryology; Aortic Aneurysm, Thoracic - genetics; Aortic Aneurysm, Thoracic - metabolism; Aortic Aneurysm, Thoracic - physiopathology; Cardiovascular; Disease Progression; Extracellular Matrix - metabolism; Extracellular matrix remodeling; Genetic Predisposition to Disease; Heredity; Humans; Matrix metalloproteinases; Matrix Metalloproteinases - metabolism; Pedigree; Phenotype; Prognosis; Risk Factors; Thoracic Aortic Aneurysm; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-beta; extracellular signal-regulated kinase; Matrix metalloproteinases; tissue plasminogen activator; transforming growth factor beta; Transforming growth factor-beta; abdominal aortic aneurysm; thoracic aortic aneurysm; transforming growth factor beta receptor 1 & 2; TGF-β; AngII; AT1; t-PA; AAA; angiotensin receptor 1; Extracellular matrix remodeling; TGF-βR1 & 2; ECM; MMP; TAA; angiotensin II; matrix metalloproteinase; VSMC; vascular smooth muscle cell; extracellular matrix; ERK; Thoracic Aortic Aneurysm
• ISSN: 0033-0620; 1532-8643; 1873-1740
• DOI: 10.1016/j.pcad.2013.04.002

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.