Strong Signs for a Weak Wall in Tricuspid Aortic Valve Associated Aneurysms and a Role for Osteopontin in Bicuspid Aortic Valve Associated Aneurysms

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...

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Published in:	International journal of molecular sciences 2019-09, Vol.20 (19), p.4782
Main Authors:	Stern, Christian, Scharinger, Bernhard, Tuerkcan, Adrian, Nebert, Clemens, Mimler, Teresa, Baranyi, Ulrike, Doppler, Christian, Aschacher, Thomas, Andreas, Martin, Stelzmueller, Marie-Elisabeth, Ehrlich, Marek, Graf, Alexandra, Laufer, Guenther, Bernhard, David, Messner, Barbara
Format:	Article
Language:	eng
Subjects:	Actin Actins - metabolism Adult Aged alpha smooth muscle actin Aneurysms Aorta Aortic Aneurysm, Thoracic - etiology Aortic Aneurysm, Thoracic - metabolism Aortic Aneurysm, Thoracic - pathology Aortic aneurysms Aortic valve Aortic Valve - abnormalities Aortic Valve - metabolism Aortic Valve - pathology Arteriosclerosis Atherosclerosis bicuspid Bicuspid Aortic Valve Disease Biomedical materials Calcification Calcification (ectopic) Calcinosis Cardiovascular disease Collagen Contraction Coronary vessels Degeneration Female Fibroblasts Fibroblasts - metabolism Fluorescence focal elastic fiber loss Gene Expression Heart Valve Diseases - metabolism Heart Valve Diseases - pathology Heart valves Histochemistry Humans Hypotheses Immunohistochemistry Male Middle Aged Muscle contraction Muscles Myocytes, Smooth Muscle - metabolism Osteopontin Osteopontin - genetics Osteopontin - metabolism Pathogenesis Population Smooth muscle Thickness Thorax tricuspid Tricuspid Valve - metabolism Tricuspid Valve - pathology
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Summary:	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.
ISSN:	1422-0067 1661-6596 1422-0067