B002 Proprotein convertase sublitisin kexin type 9 null mice are protected from postprandial triglyceridemia

IntroductionProprotein convertase subtilisin kexin type 9 (PCSK9) is a natural inhibitor of the low density lipoprotein receptor (LDLR) and its deficiency confers a high level of protection against cardiovascular disease. PCSK9 is well expressed in the liver and the intestine but its precise localization and its role in the digestive tract remain unknown.ObjectivesThe aim of this study is to determine PCSK9 distribution and localization in the intestine and examine in mice whether it acts upon postprandial lipemia.Methods and ResultsIn mice, we show that PCSK9 mRNA is highly expressed all along the small intestine and colon. Confocal microscopy on human intestines showed that PCSK9 is localized mainly in the enterocyte. Similar to hepatocytes, PCSK9 was induced by statins in polarized Caco-2 cells. Upon olive oil gavage, and in spite of similar fasting triglyceridemia, PCSK9-/- mice have a dramatically decreased postprandial triglyceridemia compared with their wild type littermates (WT) (0.075g/L/h vs 0.2g/L/h, p