Transforming growth factor-β signaling in thoracic aortic aneurysm development: a paradox in pathogenesis

JA Jones, FG Spinale, JS Ikonomidis - Journal of vascular research, 2009 - karger.com
JA Jones, FG Spinale, JS Ikonomidis
Journal of vascular research, 2009karger.com
Thoracic aortic aneurysms (TAAs) are potentially devastating, and due to their asymptomatic
behavior, pose a serious health risk characterized by the lack of medical treatment options
and high rates of surgical morbidity and mortality. Independent of the inciting stimuli
(biochemical/mechanical), TAA development proceeds by a multifactorial process
influenced by both cellular and extracellular mechanisms, resulting in alterations of the
structure and composition of the vascular extracellular matrix (ECM). While the role of …
Abstract
Thoracic aortic aneurysms (TAAs) are potentially devastating, and due to their asymptomatic behavior, pose a serious health risk characterized by the lack of medical treatment options and high rates of surgical morbidity and mortality. Independent of the inciting stimuli (biochemical/mechanical), TAA development proceeds by a multifactorial process influenced by both cellular and extracellular mechanisms, resulting in alterations of the structure and composition of the vascular extracellular matrix (ECM). While the role of enhanced ECM proteolysis in TAA formation remains undisputed, little attention has been focused on the upstream signaling events that drive the remodeling process. Recent evidence highlighting the dysregulation of transforming growth factor-β (TGF-β) signaling in ascending TAAs from Marfan syndrome patients has stimulated an interest in this intracellular signaling pathway. However, paradoxical discoveries have implicated both enhanced TGF-β signaling and loss of function TGF-β receptor mutations, in aneurysm formation; obfuscating a clear functional role for TGF-β in aneurysm development. In an effort to elucidate this subject, TGF-β signaling and its role in vascular remodeling and pathology will be reviewed, with the aim of identifying potential mechanisms of how TGF-β signaling may contribute to the formation and progression of TAA.
Karger