title: Pathophysiology of aortic aneurysm: insights from human genetics and mouse models.
abstract: Aneurysms are local dilations of an artery that predispose the vessel to sudden rupture. They are often asymptomatic and undiagnosed, resulting in a high mortality rate. The predisposition to develop thoracic aortic aneurysms is often genetically inherited and associated with syndromes affecting connective tissue homeostasis. This review discusses how elucidation of the genetic causes of syndromic forms of thoracic aortic aneurysm has helped identify pathways that contribute to disease progression, including those activated by TGF-β, angiotensin II and Notch ligands. We also discuss how pharmacological manipulation of these signaling pathways has provided further insight into the mechanism of disease and identified compounds with therapeutic potential in these and related disorders.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Miller Research Building 532, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Wilson
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Miller Research Building 532, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.
authors.forename: Russell A
authors.initials: RA
authors.lastname: Gould
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Miller Research Building 532, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Gallo MacFarlane
authors.forename: Mibava Leducq
authors.initials: ML
authors.lastname: Consortium
mesh_terms: D000818:Animals; D001014:Aortic Aneurysm / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D016212:Transforming Growth Factor beta
keywords: ERK1/2; Loeys–Dietz syndrome; Marfan syndrome; Notch; Smad; TGF-β; aneurysm; angiotensin II; aorta; bicuspid aortic valve