Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves--association with low BMP antagonists and SMAD6.
Aortic valve (AV) calcification preferentially occurs on the fibrosa side while the ventricularis side remains relatively unaffected. Here, we tested the hypothesis that side-dependent activation of bone morphogenic protein (BMP) pathway in the endothelium of the ventricularis and fibrosa is associa...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3115968?pdf=render |
| _version_ | 1818481444779982848 |
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| author | Randall F Ankeny Vinod H Thourani Daiana Weiss J David Vega W Robert Taylor Robert M Nerem Hanjoong Jo |
| author_facet | Randall F Ankeny Vinod H Thourani Daiana Weiss J David Vega W Robert Taylor Robert M Nerem Hanjoong Jo |
| author_sort | Randall F Ankeny |
| collection | DOAJ |
| description | Aortic valve (AV) calcification preferentially occurs on the fibrosa side while the ventricularis side remains relatively unaffected. Here, we tested the hypothesis that side-dependent activation of bone morphogenic protein (BMP) pathway in the endothelium of the ventricularis and fibrosa is associated with human AV calcification.Human calcified AVs obtained from AV replacement surgeries and non-calcified AVs from heart transplantations were used for immunohistochemical studies. We found SMAD-1/5/8 phosphorylation (a canonical BMP pathway) was higher in the calcified fibrosa than the non-calcified fibrosa while SMAD-2/3 phosphorylation (a canonical TGFβ pathway) did not show any difference. Interestingly, we found that BMP-2/4/6 expression was significantly higher on the ventricularis endothelium compared to the fibrosa in both calcified and non-calcified AV cusps; however, BMP antagonists (crossvienless-2/BMPER and noggin) expression was significantly higher on the ventricularis endothelium compared to the fibrosa in both disease states. Moreover, significant expression of inhibitory SMAD-6 expression was found only in the non-calcified ventricularis endothelium.SMAD-1/5/8 is preferentially activated in the calcified fibrosa endothelium of human AVs and it correlates with low expression of BMP antagonists and inhibitory SMAD6. These results suggest a dominant role of BMP antagonists in the side-dependent calcification of human AVs. |
| first_indexed | 2024-12-10T11:35:09Z |
| format | Article |
| id | doaj.art-d74f9afdca09476f97627840c94b04f6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T11:35:09Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d74f9afdca09476f97627840c94b04f62022-12-22T01:50:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2096910.1371/journal.pone.0020969Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves--association with low BMP antagonists and SMAD6.Randall F AnkenyVinod H ThouraniDaiana WeissJ David VegaW Robert TaylorRobert M NeremHanjoong JoAortic valve (AV) calcification preferentially occurs on the fibrosa side while the ventricularis side remains relatively unaffected. Here, we tested the hypothesis that side-dependent activation of bone morphogenic protein (BMP) pathway in the endothelium of the ventricularis and fibrosa is associated with human AV calcification.Human calcified AVs obtained from AV replacement surgeries and non-calcified AVs from heart transplantations were used for immunohistochemical studies. We found SMAD-1/5/8 phosphorylation (a canonical BMP pathway) was higher in the calcified fibrosa than the non-calcified fibrosa while SMAD-2/3 phosphorylation (a canonical TGFβ pathway) did not show any difference. Interestingly, we found that BMP-2/4/6 expression was significantly higher on the ventricularis endothelium compared to the fibrosa in both calcified and non-calcified AV cusps; however, BMP antagonists (crossvienless-2/BMPER and noggin) expression was significantly higher on the ventricularis endothelium compared to the fibrosa in both disease states. Moreover, significant expression of inhibitory SMAD-6 expression was found only in the non-calcified ventricularis endothelium.SMAD-1/5/8 is preferentially activated in the calcified fibrosa endothelium of human AVs and it correlates with low expression of BMP antagonists and inhibitory SMAD6. These results suggest a dominant role of BMP antagonists in the side-dependent calcification of human AVs.http://europepmc.org/articles/PMC3115968?pdf=render |
| spellingShingle | Randall F Ankeny Vinod H Thourani Daiana Weiss J David Vega W Robert Taylor Robert M Nerem Hanjoong Jo Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves--association with low BMP antagonists and SMAD6. PLoS ONE |
| title | Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves--association with low BMP antagonists and SMAD6. |
| title_full | Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves--association with low BMP antagonists and SMAD6. |
| title_fullStr | Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves--association with low BMP antagonists and SMAD6. |
| title_full_unstemmed | Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves--association with low BMP antagonists and SMAD6. |
| title_short | Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves--association with low BMP antagonists and SMAD6. |
| title_sort | preferential activation of smad1 5 8 on the fibrosa endothelium in calcified human aortic valves association with low bmp antagonists and smad6 |
| url | http://europepmc.org/articles/PMC3115968?pdf=render |
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