title: A Decade of Discovery in the Genetic Understanding of Thoracic Aortic Disease.
abstract: Aortic aneurysms are responsible for a significant number of all deaths in Western countries. In this review we provide a perspective on the important progress made over the past decade in the understanding of the genetics of this condition, with an emphasis on the more frequent forms of vascular smooth muscle and transforming growth factor β (TGF-β) signalling alterations. For several nonsyndromic and syndromic forms of thoracic aortic disease, a genetic basis has now been identified, with 3 main pathomechanisms that have emerged: perturbation of the TGF-β signalling pathway, disruption of the vascular smooth muscle cell (VSMC) contractile apparatus, and impairment of extracellular matrix synthesis. Because smooth muscle cells and proteins of the extracellular matrix directly regulate TGF-β signalling, this latter pathway emerges as a key component of thoracic aortic disease initiation and progression. These discoveries have revolutionized our understanding of thoracic aortic disease and provided inroads toward gene-specific stratification of treatment. Last, we outline how these genetic findings are translated into novel pharmaceutical approaches for thoracic aortic disease.
authors.affiliation: Cardiovascular Genetics, Department of Pediatrics, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, Québec, Canada. Electronic address: gregor.andelfinger@recherche-ste-justine.qc.ca.
authors.forename: Gregor
authors.initials: G
authors.lastname: Andelfinger
authors.affiliation: Centre for Medical Genetics, University Hospital of Antwerp/University of Antwerp, Antwerp, Belgium; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Loeys
authors.affiliation: Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Hal
authors.initials: H
authors.lastname: Dietz
mesh_terms: D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis / Q000235:genetics*; D002454:Cell Differentiation; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D010641:Phenotype; D015398:Signal Transduction