Novel pharmacological strategies to prevent aortic complications in Marfan syndrome

The Marfan syndrome(MFS)is a systemic connective tissue disorder caused by mutations in the FBN1 gene.Recent molecular studies,most performed in mouse models,revealed that the MFS is more a developmental abnormality with broad and complex effects on the morphogenesis and function of multiple organ systems.FBN1 haploinsufficiency and dysregulated transforming growth factor-beta(TGF-β)signaling seem to be critical for clinical manifestations in MFS including aortic root dilatation.Aortic root aneurysm and aortic dissection represent the main causes of morbidity and mortality in MFS.Most importantly,TGF-βantagonism through angiotensin II type 1 receptor blockers(ARBs),for example losartan,has been shown to prevent and possibly reverse aortic root dilatation in a mouse model of MFS.A first human study on a small pediatric cohort confirmed those promising results in reducing the aortic root growth over a follow-up period of 12 to 47 months.So,a large multicenter trial has been set up and results should be available soon.Other therapeutic strategies which might be combined with losartan include traditionalβ-blockade,doxycyclin and statins.Such management could offer the first potential for primary prevention of clinical manifestations in MFS.