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Robertson E, Dilworth C, Lu Y, et al. Molecular mechanisms of inherited thoracic aortic disease - from gene variant to surgical aneurysm. Biophys Rev. 2014;7(1):105-115doi: 10.1007/s12551-014-0147-1.
Robertson, E., Dilworth, C., Lu, Y., Hambly, B., & Jeremy, R. (2015). Molecular mechanisms of inherited thoracic aortic disease - from gene variant to surgical aneurysm. Biophysical reviews, 7(1), 105-115. https://doi.org/10.1007/s12551-014-0147-1
Robertson, Elizabeth, et al. "Molecular mechanisms of inherited thoracic aortic disease - from gene variant to surgical aneurysm." Biophysical reviews vol. 7,1 (2015): 105-115. doi: https://doi.org/10.1007/s12551-014-0147-1
Robertson E, Dilworth C, Lu Y, Hambly B, Jeremy R. Molecular mechanisms of inherited thoracic aortic disease - from gene variant to surgical aneurysm. Biophys Rev. 2015 Mar;7(1):105-115. doi: 10.1007/s12551-014-0147-1. Epub 2014 Dec 06. PMID: 28509973; PMCID: PMC5425748.
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Biophys Rev. 2015 Mar;7(1):105-115. doi: 10.1007/s12551-014-0147-1. Epub 2014 Dec 06.

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

Biophysical reviews

Elizabeth Robertson, Candice Dilworth, Yaxin Lu, Brett Hambly, Richmond Jeremy

Affiliations

  1. Cardiology Department, Royal Prince Alfred Hospital, Sydney, Australia.
  2. Pathology Discipline and Bosch Institute, Sydney Medical School, University of Sydney, Sydney, Australia. [email protected].
  3. The University of Sydney, Level 4 West, Charles Perkins Centre D17, Sydney, NSW, 2008, Australia. [email protected].
  4. Pathology Discipline and Bosch Institute, Sydney Medical School, University of Sydney, Sydney, Australia.

PMID: 28509973 PMCID: PMC5425748 DOI: 10.1007/s12551-014-0147-1

Abstract

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.

Keywords: Aortopathy; Fibrillin; Marfan; Transforming growth factor; Vascular smooth muscle

References

  1. Am J Physiol Cell Physiol. 2011 Mar;300(3):C647-56 - PubMed
  2. Tissue Eng Part B Rev. 2010 Oct;16(5):467-91 - PubMed
  3. N Engl J Med. 2008 Jun 26;358(26):2787-95 - PubMed
  4. Circulation. 2009 Aug 11;120(6):526-32 - PubMed
  5. Cardiovasc Res. 2008 Sep 1;79(4):581-8 - PubMed
  6. J Hypertens Suppl. 1990 Dec;8(7):S113-9 - PubMed
  7. J Hypertens. 2002 Dec;20(12):2429-37 - PubMed
  8. J Struct Biol. 1998;122(1-2):119-22 - PubMed
  9. Circ Res. 1967 Jan;20(1):99-111 - PubMed
  10. Cardiol Res Pract. 2012;2012:196037 - PubMed
  11. Cell Tissue Res. 2010 Jan;339(1):71-82 - PubMed
  12. J Am Coll Cardiol. 1997 Dec;30(7):1809-12 - PubMed
  13. Micron. 2001 Apr;32(3):251-60 - PubMed
  14. N Engl J Med. 2006 Aug 24;355(8):788-98 - PubMed
  15. Am J Cardiol. 2011 Dec 15;108(12):1801-7 - PubMed
  16. J Anat. 2010 Dec;217(6):705-14 - PubMed
  17. Hum Mutat. 1997;10 (6):415-23 - PubMed
  18. J Cell Biol. 1995 May;129(4):1165-76 - PubMed
  19. Circ Res. 2004 Feb 6;94(2):175-83 - PubMed
  20. Mol Cancer Res. 2006 Mar;4(3):209-20 - PubMed
  21. Genomics. 1993 Aug;17 (2):468-75 - PubMed
  22. Circ Res. 2012 Jan 20;110(2):312-24 - PubMed
  23. Nat Genet. 2005 Mar;37(3):275-81 - PubMed
  24. J Clin Invest. 1995 Feb;95(2):874-80 - PubMed
  25. Nat Rev Cardiol. 2009 Dec;6(12):771-86 - PubMed
  26. J Biol Chem. 2009 Jun 19;284(25):16872-81 - PubMed
  27. J Cell Sci. 2010 Sep 1;123(Pt 17):3006-18 - PubMed
  28. Clin Cardiol. 2014 Nov;37(11):672-9 - PubMed
  29. Clin Sci (Lond). 2013 Jan;124(2):97-108 - PubMed
  30. Int J Oncol. 2004 Nov;25(5):1375-82 - PubMed
  31. J Biol Chem. 2009 Sep 4;284(36):24553-67 - PubMed
  32. Nature. 2002 Jan 10;415(6868):168-71 - PubMed
  33. Cytokine Growth Factor Rev. 1999 Jun;10 (2):99-117 - PubMed
  34. Br J Pharmacol. 2007 Apr;150(8):1075-83 - PubMed
  35. Am J Hum Genet. 2007 Sep;81(3):454-66 - PubMed
  36. EMBO J. 2001 Apr 2;20(7):1663-73 - PubMed
  37. Nature. 2004 Sep 16;431(7006):350-5 - PubMed
  38. J Biol Chem. 2003 Jan 24;278(4):2750-7 - PubMed
  39. Connect Tissue Res. 1998;37(1-2):121-41 - PubMed
  40. Circulation. 2001 Sep 18;104(12 Suppl 1):I282-7 - PubMed
  41. J R Soc Interface. 2012 Jun 7;9(71):1275-86 - PubMed
  42. J Am Coll Cardiol. 2010 Jun 22;55(25):2789-800 - PubMed
  43. Int J Cardiol. 2013 Oct 3;168(3):2441-6 - PubMed
  44. Int J Cardiol. 2013 Oct 25;169(1):7-16 - PubMed
  45. N Engl J Med. 2014 May 15;370(20):1920-9 - PubMed
  46. Curr Opin Cardiol. 2014 Jan;29(1):97-102 - PubMed
  47. Annu Rev Biochem. 1998;67:609-52 - PubMed
  48. Cardiology. 2012;121(1):31-42 - PubMed
  49. Curr Cardiol Rep. 2010 Mar;12 (2):99-107 - PubMed
  50. Circ J. 2013;77(4):952-8 - PubMed
  51. Am J Med Genet A. 2013 Jan;161A(1):185-91 - PubMed
  52. J Struct Biol. 2014 Sep;187(3):242-53 - PubMed
  53. Circulation. 2005 Mar 22;111(11):e150-7 - PubMed
  54. Nat Genet. 2012 Jul 08;44(8):916-21 - PubMed
  55. Circ Res. 2011 Sep 2;109(6):680-6 - PubMed
  56. Biochem Biophys Res Commun. 2008 Jul 11;371(4):713-8 - PubMed
  57. Curr Opin Cardiol. 2006 May;21(3):180-4 - PubMed
  58. J Struct Biol. 2002 Apr-May;138(1-2):130-6 - PubMed
  59. Cell Biol Int. 1996 Jan;20(1):15-27 - PubMed
  60. Nat Genet. 2003 Mar;33(3):331-2 - PubMed
  61. Circulation. 2009 Dec 22;120(25):2541-9 - PubMed
  62. Circulation. 2001 Jul 24;104(4):448-54 - PubMed
  63. Genes Dev. 2009 Sep 15;23(18):2166-78 - PubMed
  64. J Biol Chem. 2009 Feb 27;284(9):5630-6 - PubMed
  65. Cell. 2004 Jan 23;116(2):281-97 - PubMed
  66. J Clin Invest. 2014 Jan;124(1):448-60 - PubMed
  67. Nat Genet. 2003 Mar;33(3):407-11 - PubMed
  68. Annu Rev Med. 2008;59:43-59 - PubMed
  69. Eur Heart J. 2013 Dec;34(45):3491-500 - PubMed
  70. Nat Genet. 2006 Mar;38(3):343-9 - PubMed
  71. Circ Res. 2011 Oct 28;109(10):1115-9 - PubMed
  72. J Clin Invest. 2004 Dec;114(11):1586-92 - PubMed
  73. PLoS One. 2011;6(8):e23411 - PubMed
  74. Biochem Soc Trans. 2008 Apr;36(Pt 2):257-62 - PubMed
  75. Structure. 2009 May 13;17 (5):759-68 - PubMed
  76. J Biol Chem. 2009 Feb 6;284(6):3728-38 - PubMed
  77. J Cardiovasc Pharmacol. 1999;33 Suppl 1:S21-8; discussion S41-3 - PubMed
  78. Biopolymers. 2008 Feb;89(2):160-9 - PubMed
  79. Nat Med. 2007 Feb;13(2):204-10 - PubMed
  80. Genesis. 2009 Feb;47(2):115-21 - PubMed
  81. Nature. 2011 May 19;473(7347):308-16 - PubMed
  82. J Biol Chem. 1986 Mar 25;261(9):4337-45 - PubMed
  83. Cardiovasc Pathol. 2014 Sep-Oct;23(5):261-6 - PubMed
  84. Ann Cardiothorac Surg. 2013 Jan;2(1):83-91 - PubMed
  85. Hum Mutat. 2009 Oct;30(10):1406-11 - PubMed
  86. Am J Cardiol. 1998 Aug 15;82(4):474-9 - PubMed
  87. In Vitro Cell Dev Biol. 1992 Feb;28A(2):109-19 - PubMed
  88. Circulation. 2008 May 27;117(21):2802-13 - PubMed
  89. Lab Invest. 1992 May;66(5):580-8 - PubMed
  90. Am J Pathol. 2014 Sep;184(9):2586-95 - PubMed
  91. J Biol Chem. 2007 Jan 5;282(1):800-8 - PubMed
  92. Cell Death Differ. 2009 Dec;16(12):1590-8 - PubMed
  93. Circulation. 2002 Aug 20;106(8):900-4 - PubMed
  94. Am J Hum Genet. 2009 May;84(5):617-27 - PubMed
  95. N Engl J Med. 2006 Aug 24;355(8):841-4 - PubMed
  96. J Clin Invest. 2004 Jul;114(2):172-81 - PubMed
  97. Nat Rev Cardiol. 2010 May;7(5):256-65 - PubMed
  98. Cardiovasc Res. 2010 Dec 1;88(3):395-405 - PubMed
  99. Biomol Ther (Seoul). 2014 Feb;22(2):143-8 - PubMed
  100. Heart. 2011 Mar;97(6):506-13 - PubMed
  101. Heart. 2011 Aug;97(15):1206-14 - PubMed
  102. Structure. 2012 Feb 8;20(2):215-25 - PubMed
  103. Heart. 2011 Jan;97(1):66-74 - PubMed
  104. Science. 2006 Apr 7;312(5770):117-21 - PubMed
  105. Nature. 2009 Aug 6;460(7256):705-10 - PubMed
  106. Circ Res. 2010 Feb 19;106(3):583-92 - PubMed
  107. J Clin Invest. 2009 Sep;119(9):2634-47 - PubMed
  108. Nat Genet. 2011 Feb;43(2):121-6 - PubMed
  109. Circulation. 2004 Mar 30;109(12):1530-5 - PubMed
  110. J Cell Sci. 2007 Dec 15;120(Pt 24):4269-77 - PubMed
  111. Int Heart J. 2013;54(1):23-6 - PubMed

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