Mecanismos embrionários de diferenciação de precursores coronários: princípios para aplicação em terapia celular. / Embryonic mechanisms of coronary precursor differentiation: principles for cell therapy.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Coronary vessels derive from the proepicardium (PE), a structure formed by precursor of coronary vessels cells, endothelial and smooth muscle cells (CoSMC). In vivo there is a clear gap between the endothelial differentiation and the integration of CoSMC into the vascular tubes. The aim of this work was to understand the mechanisms controlling the delayed in vivo CoSMC differentiation. Based on the progressive loss of expression of raldh2, the main retinoic acid (RA) synthesizing enzyme, we explored the RA signaling as a possible candidate inhibitor of CoSMC differentiation. Using a adenoviral raldh2 expression system and in vivo inhibition of RA synthesis we showed that RA signaling act as a brake to slow CoSMC differentiation in PE-derived cells. We also identified VEGF as key factor acting on the control of CoSMC differentiation. Together our results support a model that AR and VEGF synthesis during cardiac development was co-opted to block the CoSMC differentiation of coronary precursors before an extensive endothelial network of tubes is established.

ASSUNTO(S)

retinoic acid coronary heart development molecular embryology desenvolvimento cardíaco cell therapy Ácido retinóico histology endothelium embriologia molecular terapia celular histologia vascular smooth muscle endotélio músculo liso vascular coronárias

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