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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

Ankeny, Randall F ; Thourani, Vinod H ; Weiss, Daiana ; Vega, J David ; Taylor, W Robert ; Nerem, Robert M ; Jo, Hanjoong Cardona, Pere-Joan

PloS one, 2011-06, Vol.6 (6), p.e20969-e20969 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves--association with low BMP antagonists and SMAD6
Autor: Ankeny, Randall F ; Thourani, Vinod H ; Weiss, Daiana ; Vega, J David ; Taylor, W Robert ; Nerem, Robert M ; Jo, Hanjoong
Cardona, Pere-Joan
Assuntos: Activation ; Aged ; Aged, 80 and over ; Aorta ; Aortic valve ; Aortic Valve - drug effects ; Aortic Valve - metabolism ; Atherosclerosis ; Bending stresses ; Biology ; Biomedical engineering ; Bone morphogenetic protein 2 ; Bone Morphogenetic Proteins - antagonists & inhibitors ; Calcification ; Calcification (ectopic) ; Calcinosis ; Cardiology ; Cardiovascular system ; Coronary vessels ; Cusps ; Endothelium ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; Female ; Gene expression ; Heart ; Heart surgery ; Heart transplantation ; Heart valve diseases ; Homeostasis ; Humans ; Male ; Medicine ; Middle Aged ; Noggin protein ; Phosphorylation ; Proteins ; Rheumatic heart disease ; Shear stress ; Signal transduction ; Smad protein ; Smad Proteins - metabolism ; Transforming growth factors ; Transplantation
É parte de: PloS one, 2011-06, Vol.6 (6), p.e20969-e20969
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
Conceived and designed the experiments: RFA HJ RMN VHT. Performed the experiments: RFA VHT. Analyzed the data: RFA HJ RMN VHT. Contributed reagents/materials/analysis tools: RFA HJ RMN VHT DW WRT JDV. Wrote the paper: RFA HJ RMN VHT.
Descrição: 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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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

Ankeny, Randall F ; Thourani, Vinod H ; Weiss, Daiana ; Vega, J David ; Taylor, W Robert ; Nerem, Robert M ; Jo, Hanjoong Cardona, Pere-Joan

United States: Public Library of Science

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