caa a22 4500 606242759 CHVBK 20210128101320.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s12551-014-0147-1 doi (NATIONALLICENCE)springer-10.1007/s12551-014-0147-1 Molecular mechanisms of inherited thoracic aortic disease - from gene variant to surgical aneurysm [Elektronische Daten] [Elizabeth Robertson, Candice Dilworth, 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. International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg, 2014 Marfan nationallicence Fibrillin nationallicence Transforming growth factor nationallicence Vascular smooth muscle nationallicence Aortopathy nationallicence ARB : Angiotensin II receptor blockers nationallicence BAV : Bicuspid aortic valve nationallicence ECM : Extra-cellular matrix nationallicence EDS : Ehlers-Danlos syndrome nationallicence fTAAD : Familial thoractic aortic aneurysm and dissection nationallicence LAP : Latency-associated peptide nationallicence LDS : Loeys-Dietz syndrome nationallicence LLC : Larger latent complex nationallicence LTBP : Latent TGF-β binding protein nationallicence MAGP : Microfibil-associated peptide nationallicence MFS : Marfan synfrome nationallicence MiRNA : MicroRNA nationallicence MMP : Matrix metalloproteinases nationallicence NO : Nitric oxide nationallicence SLC : Small latent complex nationallicence TAA : Thoracic aortic aneurysm nationallicence TAAD : Thoracic aortic aneurysm and dissection nationallicence TGF-β : Transforming growth factor β nationallicence TGF-βR : Transforming growth factor β receptor nationallicence TIMP : Tissue inhibitors of metalloproteinases nationallicence VSMC : Vascular smooth muscle cell nationallicence Robertson Elizabeth Cardiology Department, Royal Prince Alfred Hospital, Sydney, Australia aut Dilworth Candice Pathology Discipline and Bosch Institute, Sydney Medical School, University of Sydney, Sydney, Australia aut Lu Yaxin Pathology Discipline and Bosch Institute, Sydney Medical School, University of Sydney, Sydney, Australia aut Hambly Brett Pathology Discipline and Bosch Institute, Sydney Medical School, University of Sydney, Sydney, Australia aut Jeremy Richmond Cardiology Department, Royal Prince Alfred Hospital, Sydney, Australia aut Biophysical Reviews Springer Berlin Heidelberg 7/1(2015-03-01), 105-115 1867-2450 7:1<105 2015 7 12551 https://doi.org/10.1007/s12551-014-0147-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s12551-014-0147-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Robertson Elizabeth Cardiology Department, Royal Prince Alfred Hospital, Sydney, Australia aut NATIONALLICENCE 700 1- Dilworth Candice Pathology Discipline and Bosch Institute, Sydney Medical School, University of Sydney, Sydney, Australia aut NATIONALLICENCE 700 1- Lu Yaxin Pathology Discipline and Bosch Institute, Sydney Medical School, University of Sydney, Sydney, Australia aut NATIONALLICENCE 700 1- Hambly Brett Pathology Discipline and Bosch Institute, Sydney Medical School, University of Sydney, Sydney, Australia aut NATIONALLICENCE 700 1- Jeremy Richmond Cardiology Department, Royal Prince Alfred Hospital, Sydney, Australia aut NATIONALLICENCE 773 0- Biophysical Reviews Springer Berlin Heidelberg 7/1(2015-03-01), 105-115 1867-2450 7:1<105 2015 7 12551