Resveratrol Inhibits Aortic Root Dilatation in the Fbn1 C1039G/+ Marfan Mouse Model

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

Research output: Contribution to journalArticlepeer-review


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 factor κB-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.

Original languageEnglish (US)
Pages (from-to)1618-1626
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number8
StatePublished - Aug 1 2016


  • Marfan syndrome
  • aortic aneurysm
  • extracellular matrix
  • micro-RNAs
  • resveratrol
  • sirtuin-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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