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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The Bone Morphogenetic Protein Antagonist Gremlin Promotes Vascular Smooth Muscle Cell Apoptosis

Texto completo
Autor(es):
Maciel, Thiago Trovati [1, 2] ; Melo, Rosilene Santos [2] ; Campos, Alexandre Holthausen [1]
Número total de Autores: 3
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Albert Einstein Res & Educ Inst, BR-05651901 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Div Nephrol, BR-05651901 Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF VASCULAR RESEARCH; v. 46, n. 4, p. 325-332, 2009.
Citações Web of Science: 8
Resumo

Background: Previous studies from our laboratory demonstrated that gremlin significantly increases vascular smooth muscle cell (VSMC) proliferation and migration. The present study investigates gremlin expression in the initial stages of rat carotid balloon injury and its effects on VSMC apoptosis. Methods: Gremlin mRNA expression was evaluated in rat carotids and cultured VSMCs by quantitative PCR. Apoptosis was analyzed in A7r5 cells and rabbit primary VSMCs following gremlin gene overexpression or silencing by chromatin morphology and caspase-3 activity. Results: Vascular injury promoted a significant decrease in gremlin mRNA levels. In addition, platelet-derived growth factor, angiotensin II and transforming growth factor (TGF)-beta 1 promoted coordinated regulation of gremlin and bone morphogenetic protein (BMP)-4 expression in opposite directions according to the confluence status of VSMC culture. In A7r5 cells, gremlin overexpression was able to increase apoptosis, as demonstrated by chromatin morphology and caspase-3 activity, while BMP administration promoted opposite effects. Finally, in agreement with our results, gremlin gene silencing effectively suppressed apoptosis in A7r5 cells and rabbit VSMCs. Conclusion: Gremlin is regulated by growth factors and vascular injury and is involved in modulation of VSMC apoptosis. Modifications of gremlin expression during vascular injury may contribute to the apoptosis resistance of VSMCs. Copyright (C) 2009 S. Karger AG, Basel (AU)

Processo FAPESP: 06/00456-0 - Mecanismo de ação e função do gene Gremlin, um antagonista da via tgf-b/bmp, em células de musculatura lisa vascular in vitro e in vivo
Beneficiário:Alexandre Holthausen Campos
Linha de fomento: Auxílio à Pesquisa - Regular