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• W2034102172 abstract "Patients with Marfan syndrome have an increased risk of life-threatening aortic complications, mostly preceded by aortic dilatation. In the FBN1(C1039G/+) Marfan mouse model, losartan decreases aortic root dilatation. We recently confirmed this beneficial effect of losartan in adult patients with Marfan syndrome. The straightforward translation of this mouse model to man is reassuring to test novel treatment strategies. A number of studies have shown signs of inflammation in aortic tissue of Marfan patients. This study examined the efficacy of anti-inflammatory therapies in attenuating aortic root dilation in Marfan syndrome and compared effects to the main preventative agent, losartan.To inhibit inflammation in FBN1(C1039G/+) Marfan mice, we treated the mice with losartan (angiotensin II receptor type 1 inhibitor), methylprednisolone (corticosteroid) or abatacept (T-cell-specific inhibitor). Treatment was initiated in adult Marfan mice with already existing aortic root dilatation, and applied for eight weeks. Methylprednisolone- or abatacept-treated mice did not reveal a reduction in aortic root dilatation. In this short time frame, losartan was the only treatment that significantly reduced aorta inflammation, transforming growth factor-beta (TGF-β) signaling and aortic root dilatation rate in these adult Marfan mice. Moreover, the methylprednisolone-treated mice had significantly more aortic alcian blue staining as a marker for aortic damage.Anti-inflammatory agents do not reduce the aortic dilatation rate in Marfan mice, but possibly increase aortic damage. Currently, the most promising therapeutic drug in Marfan syndrome is losartan, by blocking the angiotensin II receptor type 1 and thereby inhibiting pSmad2 signaling." @default.
• W2034102172 created "2016-06-24" @default.
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• W2034102172 date "2014-09-19" @default.
• W2034102172 modified "2023-09-25" @default.
• W2034102172 title "No Beneficial Effect of General and Specific Anti-Inflammatory Therapies on Aortic Dilatation in Marfan Mice" @default.
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• W2034102172 doi "https://doi.org/10.1371/journal.pone.0107221" @default.
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