Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves
| Autor: | Johan Petrini, Anders Franco-Cereceda, Per Eriksson, Rui M. M. Branca, Valentina Paloschi, Jonas Fuxe, Shohreh Maleki, Lei Du, Joëlle Magné, Kjell Hultenby, Janne Lehtiö, Hanna M. Björck, Sanela Kjellqvist |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Aortic valve medicine.medical_specialty Epithelial-Mesenchymal Transition Proteome Heart Valve Diseases Hemodynamics 030204 cardiovascular system & hematology Article 03 medical and health sciences Aortic aneurysm 0302 clinical medicine Bicuspid aortic valve Aneurysm Bicuspid Aortic Valve Disease Internal medicine medicine.artery Ascending aorta medicine Humans Epithelial–mesenchymal transition Mammary Arteries Multidisciplinary Receptors Notch business.industry Mesenchymal Stem Cells medicine.disease Tunica intima Endocytosis Aortic Aneurysm 030104 developmental biology medicine.anatomical_structure Aortic Valve cardiovascular system Cardiology Tunica Intima rhoA GTP-Binding Protein business |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep35712 |
| Popis: | Individuals with a bicuspid aortic valve (BAV) are at significantly higher risk of developing aortic complications than individuals with tricuspid aortic valves (TAV) and defective signaling during the embryonic development and/or life time exposure to abnormal hemodynamic have been proposed as underlying factors. However, an explanation for the molecular mechanisms of aortopathy in BAV has not yet been provided. We combined proteomics, RNA analyses, immunohistochemistry, and electron microscopy to identify molecular differences in samples of non-dilated ascending aortas from BAV (N = 62) and TAV (N = 54) patients. Proteomic analysis was also performed for dilated aortas (N = 6 BAV and N = 5 TAV) to gain further insight into the aortopathy of BAV. Our results collectively showed the molecular signature of an endothelial/epithelial-mesenchymal (EndMT/EMT) transition-like process, associated with instability of intimal cell junctions and activation of RHOA pathway in the intima and media layers of ascending aorta in BAV patients. We propose that an improper regulation of EndMT/EMT during the spatiotemporally related embryogenesis of semilunar valves and ascending aorta in BAV individuals may result in aortic immaturity and instability prior to dilation. Exasperation of EndMT/EMT state in post embryonic life and/or exposure to non-physiological hemodynamic could lead to the aneurysm of ascending aorta in BAV individuals. |
| Databáze: | OpenAIRE |
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