Atherosclerosis and Vascular Calcification

Investigators : Thibaut Quillard, Sarah Beck, Laurent Beck, Tom Le Corvec Blandine Maurel, Olivier Espitia
PhD students : Nathan Chaté, Aude Gatinot, Manon Mary, Marc Rio
Support staff : Marie-Aude Cheminant, Corentin Lebot

Our program is divided in three axes:

Atherosclerosis and its complications remain the main cause of death worldwide. The clinical outcomes of atherosclerotic lesions (myocardial infarcts, stroke, acute ischemia of the limbs…) directly depend on their composition. Here, 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.
 

• Calcification of intimal layer or arterial walls (TQ : ANR Mineral)

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.

With a german group led by Dr Claudia Goettsch, we are coordinating a European research project aiming at deciphering the role of cytoskeleton and extracellular vesicles (EVs) trafficking and loadout in this process. We’ll more specifically investigate EVs isolated from calcified atherosclerotic lesions to identify pro-mineralizing EV subsets, and characterize their miRNA and protein content. We’ll also test the direct impact of these miRNAs on SMC mineralization in vitro and how their loading into EVs affect their functional role on vascular calcification in vitro and in vivo.

• Calcification of media layer in CKD (LB)

Medial calcifications of the arterial wall, which are associated with hyperphosphataemia in chronic kidney disease, contribute to the development of cardiovascular disease. The lack of treatment targeting vascular calcifications is partly due to the insufficient characterization of the mechanisms underlying their formation and development.

Our projects, based on new in vivo and ex vivo mouse models, aim to improve our understanding of the role of phosphate and its transporters PiT1/SLC20A1 and PiT2/SLC20A2 in these processes and to identify new molecular factors that regulate them.

PiT proteins are at the crossroad of mineralization and metabolism, a role that we previously demonstrated through our research into the relationship between the skeleton, bone vessels, and bone marrow adiposity. Deeper analysis of their involvement in adipose tissue (energy metabolism and thermogenesis) is currently ongoing through a collaborative work with Xavier Prieur (team IV).
 

Primary Familial Brain Calcification (PFBC) is a neurodegenerative disease characterized by calcium-phosphate (Ca-Pi) deposits mostly and primarily in mural cells of capillaries and arterioles (pericytes and vascular smooth muscle cells), and associated with neuropsychiatric and motor disorders, with high impact on life quality, but no specific treatment is currently available.

So far, seven genes have been associated to PFBC and account for only 50% of patients. Among these genes, two encode Pi transporters (SLC20A2 and XPR1), and two others controls the expression of Slc20a2 at the plasma membrane. However, the molecular mechanisms underlying the dysfunctional role of PFBC genes in the induction of calcification and the appearance of clinical symptoms remains unknown. By using relevant mouse models for Slc20a2 and Xpr1, our objective is to better understand the cellular and molecular mechanisms underlying the pathophysiology of PFBC disease. We also particularly focus on the roles of mural cells in brain vessel calcifications.

Learn more about our projects

• ANR MINERAL : Thibaut Quillard (2025-2027)
• ANR PARKA : Laurent Beck (2021-2025)
• SFD PiTATHER : Sarah Beck-Cormier (2023-2025)
• FRM : Sarah Beck-Cormier (2024-2027)

• Agence Nationale de la Recherche
• Fondation de l'Avenir
• Fondation pour la Recherche Médicale