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Article Publish Status: FREE
Abstract Title:

Resveratrol Inhibits Aortic Root Dilatation in the Fbn1C1039G/+ Marfan Mouse Model.

Abstract Source:

Arterioscler Thromb Vasc Biol. 2016 Aug ;36(8):1618-26. Epub 2016 Jun 9. PMID: 27283746

Abstract Author(s):

Stijntje Hibender, Romy Franken, Cindy van Roomen, Anique Ter Braake, Ingeborg van der Made, Edith E Schermer, Quinn Gunst, Maurice J van den Hoff, Esther Lutgens, Yigal M Pinto, Maarten Groenink, Aeilko H Zwinderman, Barbara J M Mulder, Carlie J M de Vries, Vivian de Waard

Article Affiliation:

Stijntje Hibender

Abstract:

OBJECTIVE: Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene. Patients with MFS are at risk of aortic aneurysm formation and dissection. Usually, blood pressure-lowering drugs are used to reduce aortic events; however, this is not sufficient for most patients. In the aorta of smooth muscle cell-specific sirtuin-1-deficient mice, spontaneous aneurysm formation and senescence are observed. Resveratrol is known to enhance sirtuin-1 activity and to reduce senescence, which prompted us to investigate the effectiveness of resveratrol in inhibition of aortic dilatation in the Fbn1(C1039G/+) MFS mouse model.

APPROACH AND RESULTS: Aortic senescence strongly correlates with aortic root dilatation rate in MFS mice. However, although resveratrol inhibits aortic dilatation, it only shows a trend toward reduced aortic senescence. Resveratrol enhances nuclear localization of sirtuin-1 in the vessel wall and, in contrast to losartan, does not affect leukocyte infiltration nor activation of SMAD2 and extracellular signal-regulated kinases 1/2 (ERK1/2). Interestingly, specific sirtuin-1 activation (SRT1720) or inhibition (sirtinol) in MFS mice does not affect aortic root dilatation rate, although senescence is changed. Resveratrol reduces aortic elastin breaks and decreases micro-RNA-29b expression coinciding with enhanced antiapoptotic Bcl-2 expression and decreased number of terminal apoptotic cells. In cultured smooth muscle cells, the resveratrol effect on micro-RNA-29b downregulation is endothelial cell and nuclear factorκB-dependent.

CONCLUSIONS: Resveratrol inhibits aortic root dilatation in MFS mice by promoting elastin integrity and smooth muscle cell survival, involving downregulation of the aneurysm-related micro-RNA-29b in the aorta. On the basis of these data, resveratrol holds promise as a novel intervention strategy for patients with MFS.

Study Type : Animal Study

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