Critical hindlimb ischemia and endothelial dysfunction

Critical hindlimb ischemia and endothelial dysfunction

  Role of endothelial cell dysfunction in the pathophysiology of critical limb ischemia

Therapeutic angiogenesis for ischemic diseases, including critical limb ischemia (CLI), was proposed as a supplement or alternative to surgical revascularization. Nevertheless, after promising results obtained in animals, it failed to demonstrate any significant effect in large human clinical trials. Our objective was to explore the pathophysiological mechanisms associated with impaired tissue repair and perfusion in patients with CLI with the aim to identify new therapeutic targets.

The main objective of this project is to explore the pathophysiological mechanisms leading to impaired tissue repair and perfusion in diabetic patients in a new model combining diabetic neuropathy and CLI with the assumption that the endothelial dysfunction caused by diabetes might represent a target of interest to promote perfusion and post-ischemic tissue repair.

We will explore the role of the Hedgehog signaling in maintaining endothelial proper function and test the therapeutic potential of targeting endothelial cell dysfunction by manipulating Hedgehog signaling.

 

Researcher involved

Marie-Ange Renault

Principal
investigator

Alain-Pierre Gadeau

Researcher
involved

Karine Latry
Eric Ducasse

Researcher
involved

Jean-Paul Delage
Thierry Couffinhal