VULNERABILITY OF PROGEROID SMOOTH MUSCLE CELLS TO ARTERIAL SHEAR STRESS IS MEDIATED BY MMP13 - Aix-Marseille Université Access content directly
Journal Articles Nature Communications Year : 2022

VULNERABILITY OF PROGEROID SMOOTH MUSCLE CELLS TO ARTERIAL SHEAR STRESS IS MEDIATED BY MMP13

Patricia Pitrez
  • Function : Author
Luis Estronca
  • Function : Author
Luis Monteiro
  • Function : Author
Guillem Colell
  • Function : Author
Helena Vazão
  • Function : Author
Deolinda Santinha
  • Function : Author
Daniel Thornton
  • Function : Author
Anne-Laure Egesipe
  • Function : Author
Tania Cavalho
  • Function : Author
Rodrigo L dos Santos
  • Function : Author
James Smith
  • Function : Author
  • PersonId : 992375
Joao-Pedro Magalhaes
  • Function : Author
Alessandro Ori
  • Function : Author
Andreia Bernardo
  • Function : Author
Xavier Nissan
Anna Rosell
  • Function : Author
Lino Ferreira
  • Function : Author

Abstract

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow shear stress. HGPS-iPSC SMCs cultured under arterial flow conditions detach from the chip after a few days of culture; this process is mediated by the upregulation of metalloprotease 13 (MMP13). Importantly, double-mutant LmnaG609G/G609GMmp13−/− mice or LmnaG609G/G609GMmp13+/+ mice treated with a MMP inhibitor show lower SMC loss in the aortic arch than controls. MMP13 upregulation appears to be mediated, at least in part, by the upregulation of glycocalyx. Our HGPS-SMCs chip represents a platform for developing treatments for HGPS individuals that may complement previous pre-clinical and clinical treatments.

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Genetics
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hal-03780360 , version 1 (10-03-2023)

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Patricia Pitrez, Luis Estronca, Luis Monteiro, Guillem Colell, Helena Vazão, et al.. VULNERABILITY OF PROGEROID SMOOTH MUSCLE CELLS TO ARTERIAL SHEAR STRESS IS MEDIATED BY MMP13. Nature Communications, 2022, 28 (1), pp.S340. ⟨10.1038/s41467-020-17901-2⟩. ⟨hal-03780360⟩

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