Academic Journal
Proteomic analysis in aortic media of patients with Marfan syndrome reveals increased activity of calpain 2 in aortic aneurysms
| العنوان: | Proteomic analysis in aortic media of patients with Marfan syndrome reveals increased activity of calpain 2 in aortic aneurysms |
|---|---|
| المؤلفون: | Pilop, C, Aregger, F, Gorman, R C, Brunisholz, R, Gerrits, B, Schaffner, T, Gorman III, J H, Mátyás, G, Carrel, T, Frey, Brigitte M |
| المصدر: | Pilop, C; Aregger, F; Gorman, R C; Brunisholz, R; Gerrits, B; Schaffner, T; Gorman III, J H; Mátyás, G; Carrel, T; Frey, Brigitte M (2009). Proteomic analysis in aortic media of patients with Marfan syndrome reveals increased activity of calpain 2 in aortic aneurysms. Circulation, 120(11):983-991. |
| بيانات النشر: | Lippincott Wiliams & Wilkins |
| سنة النشر: | 2009 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Functional Genomics Center Zurich, Systems Biology / Functional Genomics, Institute of Medical Molecular Genetics, 570 Life sciences, biology, 610 Medicine & health |
| الوصف: | BACKGROUND: Marfan syndrome (MFS) is a heritable disorder of connective tissue, affecting principally skeletal, ocular, and cardiovascular systems. The most life-threatening manifestations are aortic aneurysm and dissection. We investigated changes in the proteome of aortic media in patients with and without MFS to gain insight into molecular mechanisms leading to aortic dilatation. METHODS AND RESULTS: Aortic samples were collected from 46 patients. Twenty-two patients suffered from MFS, 9 patients had bicuspid aortic valve, and 15 patients without connective tissue disorder served as controls. Aortic media was isolated and its proteome was analyzed in 12 patients with the use of 2-dimensional difference gel electrophoresis and mass spectrometry. We found higher amounts of filamin A C-terminal fragment, calponin 1, vinculin, microfibril-associated glycoprotein 4, and myosin-10 heavy chain in aortic media of MFS aneurysm samples than in controls. Regulation of filamin A C-terminal fragmentation was validated in all patient samples by immunoblotting. Cleavage of filamin A and the calpain substrate spectrin was increased in the MFS and bicuspid aortic valve groups. Extent of cleavage correlated positively with calpain 2 expression and negatively with the expression of its endogenous inhibitor calpastatin. CONCLUSIONS: Our observation demonstrates for the first time upregulation of the C-terminal fragment of filamin A in dilated aortic media of MFS and bicuspid aortic valve patients. In addition, our results present evidence that the cleavage of filamin A is highly likely the result of the protease calpain. Increased calpain activity might explain, at least in part, histological alterations in dilated aorta. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0009-7322 |
| Relation: | https://www.zora.uzh.ch/id/eprint/19864/34/19864_Verlag_V.pdf; https://www.zora.uzh.ch/id/eprint/19864/39/MS19864_Pilop_et_al__2009.pdf; info:pmid/19720936; urn:issn:0009-7322 |
| DOI: | 10.1161/CIRCULATIONAHA.108.843516 |
| الاتاحة: | https://www.zora.uzh.ch/id/eprint/19864/ https://www.zora.uzh.ch/id/eprint/19864/34/19864_Verlag_V.pdf https://www.zora.uzh.ch/id/eprint/19864/39/MS19864_Pilop_et_al__2009.pdf https://doi.org/10.1161/CIRCULATIONAHA.108.843516 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.FBCF7AA5 |
| قاعدة البيانات: | BASE |
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Cleavage of filamin A and the calpain substrate spectrin was increased in the MFS and bicuspid aortic valve groups. Extent of cleavage correlated positively with calpain 2 expression and negatively with the expression of its endogenous inhibitor calpastatin. CONCLUSIONS: Our observation demonstrates for the first time upregulation of the C-terminal fragment of filamin A in dilated aortic media of MFS and bicuspid aortic valve patients. In addition, our results present evidence that the cleavage of filamin A is highly likely the result of the protease calpain. 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