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Stern, C; Scharinger, B; Tuerkcan, A; Nebert, C; Mimler, T; Baranyi, U; Doppler, C; Aschacher, T; Andreas, M; Stelzmueller, ME; Ehrlich, M; Graf, A; Laufer, G; Bernhard, D; Messner, B.
Strong Signs for a Weak Wall in Tricuspid Aortic Valve Associated Aneurysms and a Role for Osteopontin in Bicuspid Aortic Valve Associated Aneurysms.
Int J Mol Sci. 2019; 20(19):
Doi: 10.3390/ijms20194782
[OPEN ACCESS]
Web of Science
PubMed
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- Co-authors Med Uni Graz
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Andreas Martin
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Baranyi Ulrike
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Nebert Clemens
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- Abstract:
- Central processes in the pathogenesis of TAV- (tricuspid aortic valve) and BAV- (bicuspid aortic valve) associated ascending thoracic aortic aneurysm (ATAA) development are still unknown. To gain new insights, we have collected aortic tissue and isolated smooth muscle cells of aneurysmal tissue and subjected them to in situ and in vitro analyses. We analyzed aortic tissue from 78 patients (31 controls, 28 TAV-ATAAs, and 19 BAV-ATAAs) and established 30 primary smooth muscle cell cultures. Analyses included histochemistry, immuno-, auto-fluorescence-based image analyses, and cellular analyses including smooth muscle cell contraction studies. With regard to TAV associated aneurysms, we observed a strong impairment of the vascular wall, which appears on different levels-structure and dimension of the layers (reduced media thickness, increased intima thickness, atherosclerotic changes, degeneration of aortic media, decrease of collagen, and increase of elastic fiber free area) as well as on the cellular level (accumulation of fibroblasts/myofibroblasts, and increase in the number of smooth muscle cells with a reduced alpha smooth muscle actin (α-SM actin) content per cell). The pathological changes in the aortic wall of BAV patients were much less pronounced-apart from an increased expression of osteopontin (OPN) in the vascular wall which stem from smooth muscle cells, we observed a trend towards increased calcification of the aortic wall (increase significantly associated with age). These observations provide strong evidence for different pathological processes and different disease mechanisms to occur in BAV- and TAV-associated aneurysms.
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Actins - metabolism
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Adult - administration & dosage
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Aged - administration & dosage
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Aortic Aneurysm, Thoracic - etiology, metabolism, pathology
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Aortic Valve - abnormalities, metabolism, pathology
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Bicuspid Aortic Valve Disease - administration & dosage
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Calcinosis - administration & dosage
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Female - administration & dosage
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Fibroblasts - metabolism
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Gene Expression - administration & dosage
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Heart Valve Diseases - metabolism, pathology
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Humans - administration & dosage
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Immunohistochemistry - administration & dosage
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Male - administration & dosage
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Middle Aged - administration & dosage
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Myocytes, Smooth Muscle - metabolism
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Osteopontin - genetics, metabolism
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Tricuspid Valve - metabolism, pathology
- Find related publications in this database (Keywords)
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osteopontin
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alpha smooth muscle actin
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focal elastic fiber loss
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atherosclerosis
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bicuspid
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tricuspid