Biophysical Reviews

, Volume 7, Issue 1, pp 105–115 | Cite as

Molecular mechanisms of inherited thoracic aortic disease – from gene variant to surgical aneurysm

  • Elizabeth Robertson
  • Candice DilworthEmail author
  • Yaxin Lu
  • Brett Hambly
  • Richmond Jeremy


Aortic dissection is a catastrophic event that has a high mortality rate. Thoracic aortic aneurysms are the clinically silent precursor that confers an increased risk of acute aortic dissection. There are several gene mutations that have been identified in key structural and regulatory proteins within the aortic wall that predispose to thoracic aneurysm formation. The most common and well characterised of these is the FBN1 gene mutation that is known to cause Marfan syndrome. Others less well-known mutations include TGF-β1 and TGF-β2 receptor mutations that cause Loeys–Dietz syndrome, Col3A1 mutations causing Ehlers–Danlos Type 4 syndrome and Smad3 and-4, ACTA2 and MYHII mutations that cause familial thoracic aortic aneurysm and dissection. Despite the variation in the proteins affected by these genetic mutations, there is a unifying pathological end point of medial degeneration within the wall of the aorta characterised by vascular smooth muscle cell loss, fragmentation and loss of elastic fibers, and accumulation of proteoglycans and glycosaminoglycans within vascular smooth muscle cell-depleted areas of the aortic media. Our understanding of these mutations and their post-translational effects has led to a greater understanding of the pathophysiology that underlies thoracic aortic aneurysm formation. Despite this, there are still many unanswered questions regarding the molecular mechanisms. Further elucidation of the signalling pathways will help us identify targets that may be suitable modifiers to enhance treatment of this often fatal condition.


Marfan Fibrillin Transforming growth factor Vascular smooth muscle Aortopathy 



Angiotensin II receptor blockers


Bicuspid aortic valve


Extra-cellular matrix


Ehlers–Danlos syndrome


Familial thoractic aortic aneurysm and dissection


Latency-associated peptide


Loeys–Dietz syndrome


Larger latent complex


Latent TGF-β binding protein


Microfibil-associated peptide


Marfan synfrome




Matrix metalloproteinases


Nitric oxide


Small latent complex


Thoracic aortic aneurysm


Thoracic aortic aneurysm and dissection


Transforming growth factor β


Transforming growth factor β receptor


Tissue inhibitors of metalloproteinases


Vascular smooth muscle cell



We do not have any acknowledgements to make. This article does not contain any studies with animals performed by any of the authors. This article does not contain any studies with human participants performed by any of the authors.

All authors declare no conflict of interest

Elizabeth Robertson declares no conflict of interest. Candice Dilworth declares no conflict of interest. Yaxin Lu declares no conflict of interest. Brett Hambly declares no conflict of interest. Richmond Jeremy declares no conflict of interest.


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© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Elizabeth Robertson
    • 1
  • Candice Dilworth
    • 2
    • 3
    Email author
  • Yaxin Lu
    • 2
  • Brett Hambly
    • 2
  • Richmond Jeremy
    • 1
  1. 1.Cardiology DepartmentRoyal Prince Alfred HospitalSydneyAustralia
  2. 2.Pathology Discipline and Bosch Institute, Sydney Medical SchoolUniversity of SydneySydneyAustralia
  3. 3.The University of SydneySydneyAustralia

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