A decade of discovery in the genetic understanding of thoracic aortic diseaseA decade of discovery in the genetic understanding of thoracic aortic disease
Faculty of Medicine and Health Sciences
Medical Genetics (MEDGEN)
2016New york :Elsevier science inc, 2016
Canadian journal of cardiology. - Oakville, Ont.
32(2016):1, p. 13-25
University of Antwerp
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 b (TGF-beta) 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-beta signalling pathway, disruption of the vascular smooth muscle cell (VSMC) contractile apparatus, and impairment of extra-cellular matrix synthesis. Because smooth muscle cells and proteins of the extracellular matrix directly regulate TGF-beta 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.