• Le 02 July 2020
    A huis clos
  • 14h00 

Titre de la thèse : Intestinal role and beyond cholesterol metabolism of PCSK9

Equipe

Equipe IV -  Dyslipidemias and lipotoxicity


Directeur de thèse

Bertrand CARIOU

Co-encadrant

Cédric LE MAY


Jury

  • Pr René VALÉRO, PU-PH, UMR 1062 Inserm/1260 Inra - Marseille (Président du jury)
  • Dr Sophie LESTAVEL, PU, U1011 - Lille (rapporteur)
  • Dr Lauren YVAN-CHARVET, DR, U1065 - Nice (rapporteur)
  • Dr Sandrine MÉNARD, CR, UMR 1331 Toxalim - Toulouse (examinateur)
  • Dr Catherine MARTEL, PU, Institut de Cardiologie - Montréal (examinateur)


Résumé

PCSK9 (ProProtein Convertase Subtilisin Kexin Type 9) is the 3rd gene responsible for familial hypercholesterolemia. Indeed, PCSK9 is a natural inhibitor of the LDL receptor. Patients with PCSK9 gain function mutations are at very high risk for cardiovascular disease. In addition to its impact on cholesterol metabolism, PCSK9 plays a role in another cardiovascular risk factor: postprandial lipemia. This phenomenon, characterized by a rise in plasma triglycerides after a meal, is a risk factor for cardiovascular disease in certain pathologies, particularly in patients with type 2 diabetes. It has been shown that mouse models deficient in PCSK9 have a reduction in their postprandial lipemia. During my thesis, we showed by using deficient mouse models that inhibition of PCSK9 by anti-PCSK9 antibodies and the development of an original model of intestinal PCSK9 deficiency that the circulating form of PCSK9 is crucial in the phenomenon of postprandial lipemia. Beyond lipid metabolism, PCSK9 has been shown to play a role in inflammatory responses, particularly during septic shock. In my thesis, we observed the impact of PCSK9 deficiency and inhibition on the food allergy development. We showed that the absence of PCSK9 protects against the onset of allergy symptoms. My thesis has therefore highlighted the role of PCSK9 beyond cholesterol metabolism and at the intestinal level.