A role for the endothelium in vascular calcification.
Circ Res
; 113(5): 495-504, 2013 Aug 16.
Article
em En
| MEDLINE
| ID: mdl-23852538
ABSTRACT
RATIONALE Vascular calcification is a regulated process that involves osteoprogenitor cells and frequently complicates common vascular disease, such as atherosclerosis and diabetic vasculopathy. However, it is not clear whether the vascular endothelium has a role in contributing osteoprogenitor cells to the calcific lesions. OBJECTIVE:
To determine whether the vascular endothelium contributes osteoprogenitor cells to vascular calcification. METHODS ANDRESULTS:
In this study, we use 2 mouse models of vascular calcification, mice with gene deletion of matrix Gla protein, a bone morphogenetic protein (BMP)-inhibitor, and Ins2Akita/+ mice, a diabetes model. We show that enhanced BMP signaling in both types of mice stimulates the vascular endothelium to contribute osteoprogenitor cells to the vascular calcification. The enhanced BMP signaling results in endothelial-mesenchymal transitions and the emergence of multipotent cells, followed by osteoinduction. Endothelial markers colocalize with multipotent and osteogenic markers in calcified arteries by immunostaining and fluorescence-activated cell sorting. Lineage tracing using Tie2-Gfp transgenic mice supports an endothelial origin of the osteogenic cells. Enhancement of matrix Gla protein expression in Ins2Akita/+ mice, as mediated by an Mgp transgene, limits the generation of multipotent cells. Moreover, matrix Gla protein-depleted human aortic endothelial cells in vitro acquire multipotency rendering the cells susceptible to osteoinduction by BMP and high glucose.CONCLUSIONS:
Our data suggest that the endothelium is a source of osteoprogenitor cells in vascular calcification that occurs in disorders with high BMP activation, such as deficiency of BMP-inhibitors and diabetes mellitus.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doenças Vasculares
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Calcinose
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Proteínas de Ligação ao Cálcio
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Endotélio Vascular
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Proteínas da Matriz Extracelular
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Células-Tronco Multipotentes
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Células Endoteliais
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Angiopatias Diabéticas
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Transdiferenciação Celular
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Insulina
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article