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Loeys-Dietz Syndrome Associated With a Higher Risk of Aortic Aneurysm

by Dr. Enozia Vakil on December 22, 2013 at 10:07 PM
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 Loeys-Dietz Syndrome Associated With a Higher Risk of Aortic Aneurysm

Aortic aneurysm may be a risk factor for those with Loeys-Dietz syndrome. LDS results in the presence of missense mutations within either of the genes encoding receptors for TGF-β. LDS-associated mutations are predicted to reduce TGF-β signaling; however, aortic tissue samples from LDS patients indicate that TGF-β signaling may be enhanced.

In this issue of the Journal of Clinical Investigation, Harry Dietz and colleagues at Johns Hopkins School of Medicine developed a mouse model of LDS, in which transgenic animals expressing Tgfbr1 or Tgfbr2 with LDS-associated mutations recapitulated human phenotypes. Using this model, the authors determined that even though the mutated TGF-β receptors were functionally defective, there was evidence of increased TGF-β signaling as indicated by elevated Smad2 phosphorylation. Furthermore, development of aortic aneurysms in these mice was ameliorated by treatment with an Angiotensin II type 1 (AT1) receptor antagonist. In a companion commentary, Alan Daughtery and colleagues at the University of Kentucky discuss the therapeutic implications of this study on the use of AT1 receptor agonists to treat LDS-associated aneurism.

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Source: Eurekalert

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