title: Proprotein convertase subtilisin kexin type 9 null mice are protected from postprandial triglyceridemia.
abstract: OBJECTIVE
  Proprotein convertase subtilisin kexin type 9 (PCSK9) is a natural inhibitor of the low-density lipoprotein receptor, and its deficiency in humans results in low plasma LDL-cholesterol and protection against cardiovascular disease. We explored whether PCSK9 expression impacts postprandial triglyceridemia, another important cardiovascular risk factor.
  
  
  RESULTS
  Real-time PCR and confocal microscopy were used to show that PCSK9 is expressed throughout the entire small intestine and in human enterocytes. On olive oil gavage, PCSK9-deficient mice showed a dramatically decreased postprandial triglyceridemia compared with their wild-type littermates. Lymph analysis revealed that intestinal TG output is not quantitatively modified by PCSK9 deletion. However, PCSK9-/- mice present with a significant reduction of lymphatic apoB secretion compared to PCSK9+/+ mice. Modulating PCSK9 expression in polarized CaCo-2 cells confirmed the relationship between PCSK9 and apoB secretion; PCSK9-/- mice consistently secrete larger TG-rich lipoprotein than wild-type littermates. Finally, kinetic studies showed that PCSK9-deficient mice have an increased ability to clear chylomicrons compared to wild-type littermates.
  
  
  CONCLUSIONS
  These findings indicate that in addition to its effect on LDL-cholesterol, PCSK9 deficiency might protect against cardiovascular disease by reducing postprandial triglyceridemia.
authors.affiliation: INSERM U915, CHU de Nantes, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Le May
authors.forename: Sanae
authors.initials: S
authors.lastname: Kourimate
authors.forename: Cédric
authors.initials: C
authors.lastname: Langhi
authors.forename: Maud
authors.initials: M
authors.lastname: Chétiveaux
authors.forename: Anne
authors.initials: A
authors.lastname: Jarry
authors.forename: Christine
authors.initials: C
authors.lastname: Comera
authors.forename: Xavier
authors.initials: X
authors.lastname: Collet
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
authors.forename: Michel
authors.initials: M
authors.lastname: Krempf
authors.forename: Bertrand
authors.initials: B
authors.lastname: Cariou
authors.forename: Philippe
authors.initials: P
authors.lastname: Costet
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D018938:Caco-2 Cells; D002914:Chylomicrons / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism*; D020397:Goblet Cells / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
chemical_list: D001055:Apolipoproteins B; D002914:Chylomicrons; D014280:Triglycerides; C472126:Pcsk9 protein, mouse; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases