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Loeys, Bart L.
Drug discovery today, 02/2015, Volume: 20, Issue: 2Journal Article
•Study of Marfan mouse models revealed a key role for TGFβ signaling in the pathogenesis of aortic aneurysm.•Canonical and noncanonical TGFβ signaling play parts in aortic aneurysm formation.•Losartan has TGFβ blocking effects as well as hemodynamic effects. The study of mouse models for Marfan syndrome, an autosomal dominant connective tissue disorder caused by mutations in fibrillin-1 (FBN1), has shifted our understanding of the pathogenesis of thoracic aortic aneurysm significantly. Multiple lines of evidence support the notion that dysregulation of canonical and noncanonical transforming growth factor (TGF)β signaling is the responsible pathway in this and related thoracic aortic aneurysm conditions. This exciting knowledge has opened numerous new treatment options, including antagonism of the angiotensin II receptor blocker type 1 (AT1R). In this review, we summarize the current knowledge, the first human losartan Marfan trial results and future therapeutic perspectives for aortic disease in Marfan patients.
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