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Gestational stress induces the unfolded protein response, resulting in heart defects.
Shi, Hongjun; O'Reilly, Victoria C; Moreau, Julie L M; Bewes, Therese R; Yam, Michelle X; Chapman, Bogdan E; Grieve, Stuart M; Stocker, Roland; Graham, Robert M; Chapman, Gavin; Sparrow, Duncan B; Dunwoodie, Sally L.
Afiliación
  • Shi H; The Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • O'Reilly VC; The Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia.
  • Moreau JL; The Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia.
  • Bewes TR; The Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia.
  • Yam MX; The Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia.
  • Chapman BE; School of Molecular Bioscience, University of Sydney, Sydney, New South Wales 2006, Australia.
  • Grieve SM; School of Molecular Bioscience, University of Sydney, Sydney, New South Wales 2006, Australia Sydney Translational Imaging Laboratory, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia Department of Radiology, Royal Prince Alfred Hospital, Sydney, New South Wales 2
  • Stocker R; The Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Graham RM; The Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New Sout
  • Chapman G; The Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Sparrow DB; The Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia s.dunwoodie@victorchang.edu.au duncan.sparrow@dpag.ox.ac.uk.
  • Dunwoodie SL; The Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New Sout
Development ; 143(14): 2561-72, 2016 07 15.
Article en En | MEDLINE | ID: mdl-27436040
ABSTRACT
Congenital heart disease (CHD) is an enigma. It is the most common human birth defect and yet, even with the application of modern genetic and genomic technologies, only a minority of cases can be explained genetically. This is because environmental stressors also cause CHD. Here we propose a plausible non-genetic mechanism for induction of CHD by environmental stressors. We show that exposure of mouse embryos to short-term gestational hypoxia induces the most common types of heart defect. This is mediated by the rapid induction of the unfolded protein response (UPR), which profoundly reduces FGF signaling in cardiac progenitor cells of the second heart field. Thus, UPR activation during human pregnancy might be a common cause of CHD. Our findings have far-reaching consequences because the UPR is activated by a myriad of environmental or pathophysiological conditions. Ultimately, our discovery could lead to preventative strategies to reduce the incidence of human CHD.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Estrés Fisiológico / Respuesta de Proteína Desplegada / Cardiopatías Congénitas Límite: Animals / Pregnancy Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Australia
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Estrés Fisiológico / Respuesta de Proteína Desplegada / Cardiopatías Congénitas Límite: Animals / Pregnancy Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Australia