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Post-doc Project: Mechanobiology of aneurysm of abdominal aorta

Starting: November 2013

 

Aneurysm of the abdominal aorta (AAA) is a common and frequently lethal age-related disease affecting 6 to 9% of the population over the age of 65. The formation of AAA is believed to be a multi-factorial and degenerative process resulting from a complex interplay between biological processes in the arterial wall and the hemodynamic stimuli exerted on the wall, such as wall shear stress. As a monolayer in direct contact with blood, vascular endothelial cells are the primary cells exposed to this stress. 

The aim of this project is to investigate the role of hemodynamic forces, in particular spatio-temporal wall shear stress gradients, on endothelial cell dysfunction and consequently on the AAA wall remodelling.

This project is based on real and numerical experimentations aiming to:

  • develop a new device allowing to reproduce wall shear stress encountered at different locations of the aneurismal sac on endothelial cells within dedicated flow chambers;
  • design an AAA model in order to simulate and study the effect of spatio-temporal wall shear stress gradients.

Shear flow effect on the morphology of cells (on left: control experiment; on right: after 18 hrs of wall shear stress; scale bar = 100 µm)

To clarify the role of the shear stress gradient in endothelial cell dysfunction, the cells will be analyzed for several biological aspects in both experimental setups. The above experiments will be coupled with real-time microscopy observations, and biological measurements such as matrix metalloproteinases levels of expression, and nitric oxide concentrations.

 

This project involves a collaboration between the Laboratoire Interdisciplinaire de Physique, the 3SR laboratory, the Institut Albert Bonniot, and the IRPHE institute of Marseille.

 

PI: Claude Verdier; Co-PI: Christian GeindreauPost-doc researcher: Stephanie Traub (view her CV)

 

Project update

Published in 2014: Macek Jilkova ZLisowska J, Manet S, Verdier C, Deplano V, Geindreau C, Faurobert E, Albiges-Rizo C, Duperray A. CCM proteins control endothelial beta 1 integrin dependant response to shear stress, Biology Open 3(12), 1228-1235 (2014). Read the online version

 

Published in 2013: Macek-Jilkova Z, Deplano V, Verdier C, Toungara M, Geindreau C, Duperray A. Wall shear stress and endothelial cells dysfunction in the context of abdominal aortic aneurysms, Comput. Methods Biomechanics Biomed. Eng., 16 supp. 1, 27-29 (2013). Read the online version

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