Oxytocin antagonism prevents pregnancy-associated aortic dissection in a mouse model of Marfan syndrome.

Autor:	Habashi JP; Division of Pediatric Cardiology, Johns Hopkins University, Baltimore, MD 21287, USA., MacFarlane EG; Center for Medical Genetics, Johns Hopkins University, Baltimore, MD 21287, USA., Bagirzadeh R; Center for Medical Genetics, Johns Hopkins University, Baltimore, MD 21287, USA., Bowen C; Center for Medical Genetics, Johns Hopkins University, Baltimore, MD 21287, USA., Huso N; Center for Medical Genetics, Johns Hopkins University, Baltimore, MD 21287, USA., Chen Y; Center for Medical Genetics, Johns Hopkins University, Baltimore, MD 21287, USA., Bedja D; Division of Comparative Medicine, Johns Hopkins University, Baltimore, MD 21287, USA., Creamer TJ; Department of Surgery, Johns Hopkins University, Baltimore, MD 21287, USA., Rykiel G; Center for Medical Genetics, Johns Hopkins University, Baltimore, MD 21287, USA., Manning M; Department of Cancer Biology, University of Toledo College of Medicine, Toledo, OH 43614, USA., Huso D; Division of Comparative Medicine, Johns Hopkins University, Baltimore, MD 21287, USA., Dietz HC; Center for Medical Genetics, Johns Hopkins University, Baltimore, MD 21287, USA. hdietz@jhmi.edu.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2019 May 01; Vol. 11 (490).
DOI:	10.1126/scitranslmed.aat4822
Abstrakt:	Women with Marfan syndrome (MFS) are at high risk for pregnancy-associated aortic dissection. Pathogenic models that singularly invoke hemodynamic stress are difficult to reconcile with predominant postnatal occurrence of aortic tear, often occurring weeks to months after delivery. In consideration of events that peak at term, are sustained after delivery, and might synergize with previously defined signaling pathways implicated in aneurysm progression, we examined the hormone oxytocin, which initiates uterine contraction and milk letdown for the duration of lactation through phosphorylation of extracellular signal-regulated kinase (ERK). In a mouse model of MFS that shows highly penetrant postnatal aortic dissection, risk was strongly attenuated by preventing lactation or use of an oxytocin receptor antagonist. Survival correlated inversely with the extent of ERK activation in the aortic wall, and strong protection was observed upon attenuation of ERK phosphorylation using an inhibitor of ERK kinase (MEK) or the U.S. Food and Drug Administration-approved medication hydralazine, offering potential therapeutic strategies for pregnancy-associated vascular catastrophe in the setting of MFS. (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu