New pathways in lipoprotein metabolism

Cédric Le May

Membres de l’axe thématique IV-1 :
Claire Blanchard, Bertrand Cariou, Cédric Le May, Antoine Rimbert, Sarra Smati-Grangeon
Victoria Lorant, Thibaud Sotin, Samuel Frey
Lucie Arnaud, Audrey Ayer, Lise Bray, Amandine Caillaud, Aurore Girardeau, Adeline Goudal, Murielle Patittuci

My group mainly focuses on the identification of new physiological and molecular pathways in lipoprotein metabolism and cardiovascular (CV) diseases.

Amongst CV risk factors, LDL-cholesterol (LDL-C) plays a critical role in the development of atherosclerosis. Indeed, clinical trials have clearly demonstrated that targeting the LDL-C is the most efficient way to reduce CV events and atherosclerosis development. In addition, large meta-analyses highlighted that there is a clear relationship between the degree of absolute LDL-C lowering and the degree of CV event reduction. Consequently, LDL-C reduction is the primary target to reduce cardiac events. Therefore, the main goal of our group is to better decipher the hepatic and intestinal metabolism of LDL in order to identify new pathways and ultimately propose new drug targets for hypercholesterolemia.

During the 2022-2027 period; I will lead the axis « New pathways in lipoprotein metabolism ». The scientific program will be divided in two interconnected major parts: the first is a genetic strategy to identify novel drug targets in ASCVD beyond LDL-C lowering (i.e., by focusing on atheroprotective factors in FH) while the second will focus on the functional characterization of identified targets.

 

Identification of a Gain-of-Function LIPC Variant as a Novel Cause of Familial Combined Hypocholesterolemia. Dijk W, Di Filippo M, Kooijman S, van Eenige R, Rimbert A, Caillaud A, Thedrez A, Arnaud L, Pronk A, Garçon D, Sotin T, Lindenbaum P, Garcia EO, Pais de Barros J-P, Duvillard L, Si-Tayeb K, Amigo N, Le Questel J-Y, Rensen PCN, Le May C, Moulin P, Cariou B. Circulation 2022;101161CIRCULATIONAHA121057978.doi:10.1161/CIRCULATIONAHA.121.057978.

PCSK9 regulates the NODAL signaling pathway and cellular proliferation in hiPSCs. Roudaut M, Idriss S, Caillaud A, Girardeau A, Rimbert A, Champon B, David A, Lévêque A, Arnaud L, Pichelin M, Prieur X, Prat A, Seidah NG, Zibara K, Le May C, Cariou B, Si-Tayeb K.Stem Cell Reports. 2021 Dec 14;16(12):2958-2972. doi: 10.1016/j.stemcr.2021.10.004.

PCSK9 is not secreted from mature differentiated intestinal cells. François M, Thédrez A, Garçon D, Ayer A, Sotin T, Dijk W, Blanchard C, Chadeuf G, Arnaud L, Croyal M, Van Landeghem L, Touvron M, Prieur X, Roubtsova A, Seidah N, Prat A, Cariou B, Le May C.J Lipid Res. 2021;62:100096. doi: 10.1016/j.jlr.2021.100096.

Routine use of statins and increased COVID-19 related mortality in inpatients with type 2 diabetes: Results from the CORONADO study. Cariou B, Goronflot T, Rimbert A, Boullu S, Le May C, Moulin P, Pichelin M, Potier L, Smati S, Sultan A, Tramunt B, Wargny M, Gourdy P, Hadjadj S; CORONADO investigators.Diabetes Metab. 2021 Mar;47(2):101202. doi: 10.1016/j.diabet.2020.10.001
 
Genetic Inhibition of PCSK9 and Liver Function. Rimbert A, Smati S, Dijk W, Le May C, Cariou B.JAMA Cardiol. 2021 Mar 1;6(3):353-354. doi: 10.1001/jamacardio.2020.5341.

Circulating Rather Than Intestinal PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Regulates Postprandial Lipemia in Mice. Garçon D, Moreau F, Ayer A, Dijk W, Prieur X, Arnaud L, Roubtsova A, Seidah N, Prat A, Cariou B, Le May C.Arterioscler Thromb Vasc Biol. 2020 Sep;40(9):2084-2094. doi: 10.1161/ATVBAHA.120.314194.
 

Funding

This programme has been supported by :
 

• ANR
• Amgen
• Fondation Genavie
• Fondation de France
• Fondation pour la Recherche Médicale
• Institut de Recherche en Santé Respiratoire des Pays de la Loire

 

• NEXT
• Pfizer
• Transatlantic Leducq Network