2 research outputs found
ARAVU (AGE-RAGE and Uremic vasculopathy) - Role of the AGE-RAGE interaction in a model of vascular aging : uremic vasculopathy.
Les eĢveĢnements cardiovasculaires sont la premieĢre cause de mortaliteĢ chez les patients insuffisants reĢnaux chroniques. Ces complications font suite aĢ des modifications structurelles et fonctionnelles de la paroi vasculaire regroupeĢes sous le terme de vasculopathie ureĢmique. ParalleĢlement aĢ ces modifications vasculaires, lāureĢmie sāaccompagne dāune accumulation de substances non eĢpureĢes par le rein appeleĢes toxines ureĢmiques, telles que les produits de la glycation avanceĢe (AGEs) ou les ligands de RAGE. Ces toxines peuvent interagir avec leur reĢcepteur, RAGE, qui est pro- inflammatoire et impliqueĢ dans le remodelage arteĢriel. Cette theĢse a consisteĢ en lāeĢtude, chez la souris, du roĢle de lāaccumulation des ligands de RAGE et de leur interaction avec celui-ci dans le deĢveloppement de lāatheĢroscleĢrose, des calcifications vasculaires et de la thrombose arteĢrielle au cours de lāinsuffisance reĢnale chronique (IRC). Dans un premier temps, nous avons montreĢ que lāIRC conduisait aĢ une accumulation des AGEs et des ligands de RAGE seĢriques et tissulaires, ainsi quāune augmentation de lāexpression de RAGE au sein de la paroi vasculaire participant aĢ la formation des plaques dāatheĢrome. Dans un second temps, nous avons deĢmontreĢ que RAGE participait aux calcifications vasculaires favorisant lāexpression de co-transporteur de phosphate inorganique (Pit-1), induisant la diffeĢrenciation des cellules musculaires lisses en cellules Ā« osteoblast-like Ā». Enfin, nous avons montreĢ que RAGE participait aĢ la formation dāun thrombus arteĢriel duĢ aĢ une hyperactiviteĢ plaquettaire. En conclusion, cette theĢse a permis de renforcer le concept que lāaxe ligands de RAGE/RAGE est un acteur important dans la vasculopathie ureĢmique.Cardiovascular events are the primary cause of morbidity and mortality in chronic kidney disease patients. These complications are due to structural and functional changes in the vascular wall named uraemic vasculopathy. Alongside these vascular changes, uremia is accompanied by the retention of various solutes that are normally excreted by the kidneys called uremic toxins, such as the products of advanced glycation (AGEs) or the ligands of RAGE. These toxins may interact with their receptor, RAGE, which is pro-inflammatory and involved in arterial remodeling. The aim of this thesis was to study, in mice, the role of the accumulation of RAGE ligands and their interaction with it in the development of atherosclerosis, vascular calcification and arterial thrombosis in chronic renal failure (CKD). Initially, we showed that CKD leads to an accumulation of serum and tissue AGEs and RAGE ligands, as well as an increase in RAGE expression in the vascular wall involved in atheroma plaque formation. Secondly, we have demonstrated that RAGE is involved in vascular calcification promoting the expression of inorganic phosphate cotransporter (Pit-1), inducing the differentiation of smooth muscle cells "osteoblast-like". Finally, we showed that RAGE participated in the formation of arterial thrombus due to platelet hyperactivity. In conclusion this thesis consolidates that RAGE-RAGE ligands axis is an important actor in uremic vasculopathy