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Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves - association with low BMP antagonists and SMAD6

Title
Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves - association with low BMP antagonists and SMAD6
Authors
Ankeny R.F.Thourani V.H.Weiss D.Vega J.D.Taylor W.R.Nerem R.M.Jo H.
Ewha Authors
조한중
Issue Date
2011
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
PLoS ONE vol. 6, no. 6
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Background: 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. Methods and Results: 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. Conclusions: 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. © 2011 Ankeny et al.
DOI
10.1371/journal.pone.0020969
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일반대학원 > 바이오융합과학과 > Journal papers
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