Atherosclerosis and Vascular Calcification

Thibaut Quillard, Laurent Beck, Sarah Beck-Cormier, Blandine Maurel

• In our group, we aim to better understand the physiopathology of atherosclerotic plaques formation and development. Atherosclerotic plaques can present various compositions. Such differences are often found between arterial beds, notably with carotid arteries developing typically lipid-rich and inflamed lesions, while femoral arteries mostly associate with fibrous and heavily calcified lesions. Because vascular cells (endothelial and smooth muscle cells) from these anatomical locations have specific transcriptomic signatures and identities, we will investigate how cardiovascular risk factor affect carotid and femoral vascular cell phenotypes and responses, and how this further translates into differential plaque development. Identification of molecular determinants implicated in these responses will help better understand atherosclerosis development, and will provide with novel therapeutic strategies based on lesion composition and localization. Our work will also study how hemodynamics impacts vascular cells phenotype, as carotid and femoral arteries are also exposed to specific blood flow dynamics. (T. Quillard, B. Maurel)

• Calcification of atherosclerotic lesions is an independent predictive factor for cardiovascular complications and death, by affecting locally plaque stability, thrombus formation, endovascular treatment success, and more globally by greatly impacting vascular rigidity and vascular blood system resistance. In chronic kidney disease, hyperphosphatemia triggers calcification of the arterial wall which contribute to the developmentnt of cardiovascular diseases. There is still no treatment targeting this pathological process of vascular calcification in those two diseases, partly because the mechanisms underlying their formation and development are still poorly characterized. Thanks to our human biocollection of human atherosclerotic lesions and healthy arteries, and novel murine experimental models, we aim to identify new molecular players regulating this process and better understand the role(s) of the PiT1/SLC20A1 and PiT2/SLC20A2 proteins. (L. Beck, S. Beck-Cormier). These two proteins are at the cross-road of mineralization and metabolism, a role that we previously illustrated in investigating the relationship between skeleton, bone vessels and bone marrow adiposity. Deeper analysis of their involvement in adipose tissue (energy metabolism and thermogenesis) in currently ongoing through a collaboration with Xavier Prieur (team IV) (S. Beck-Cormier, L. Beck).

Funding

• ANR
• Fondation de l'Avenir
• Fondation Maladie Rare
• Genavie
• Région Pays de la Loire
• Société française de cardiologie
• Société Francophone du Diabète
• Société Française de Rhumatologie