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

Jennifer Pardo Habashi, Elena Gallo MacFarlane, Rustam Bagirzadeh, Caitlin Bowen, Nicholas Huso, Yichun Chen, Djahida Bedja, Tyler J. Creamer, Graham Rykiel, Maurice Manning, David Huso, Harry C. Dietz

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish (US)
Article numbereaat4822
JournalScience translational medicine
Issue number490
StatePublished - 2019

ASJC Scopus subject areas

  • General Medicine


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