TY - JOUR
T1 - A Decade of Discovery in the Genetic Understanding of Thoracic Aortic Disease
AU - Andelfinger, Gregor
AU - Loeys, Bart
AU - Dietz, Hal
N1 - Funding Information:
G.A. is the recipient of a Senior Clinical Research Scholar of the Fonds de Recherche du Québec-Santé. Funding is provided by the Fondation Leducq (MIBAVA [Mechanistic Interrogation of Bicuspid Aortic Valve Associated Aortopathy] network), Canadian Institutes of Health Research, and the Banque Nationale Research Chair in Cardiovascular Genetics. This research was supported by funding from the University of Antwerp (Lanceringsproject), the Fund for Scientific Research, Flanders (FWO, Belgium, G.0221.12), The Dutch Heart Foundation (2013T093), the Fondation Leducq (MIBAVA - Leducq 12CVD03). L.B. is senior clinical investigator of the Fund for Scientific Research, Flanders and holds a starting grant from the European Research Council (ERC- StG-2012-30972-BRAVE).
Publisher Copyright:
© 2016 Canadian Cardiovascular Society.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cjca.2015.10.017
DO - 10.1016/j.cjca.2015.10.017
M3 - Review article
C2 - 26724507
AN - SCOPUS:84951849274
SN - 0828-282X
VL - 32
SP - 13
EP - 25
JO - Canadian Journal of Cardiology
JF - Canadian Journal of Cardiology
IS - 1
ER -