title: Extended-Release Niacin/Laropiprant Improves Overall Efficacy of Postprandial Reverse Cholesterol Transport.
abstract: OBJECTIVE
  Postprandial atherogenic lipoproteins, characterizing high-risk patients, correlate positively with cardiovascular events. Although the effect of niacin on fasting lipids is well established, its impact on atheroprotective reverse cholesterol transport (RCT) pathway and on functional features of circulating lipoproteins during the postprandial state remains indeterminate.
  
  
  RESULTS
  We evaluated RCT pathway during postprandial phase in dyslipidemic patients displaying a low high-density lipoprotein (HDL) cholesterol phenotype. Ten subjects on stable statin therapy received 1 g/20 mg extended-release niacin/laropiprant (ERN/LRPT) for 4 weeks followed by 2 g/40 mg ERN/LRPT for additional 8 weeks. At each experimental period, postprandial hypertriglyceridemia and major steps of RCT, including cholesterol efflux from human macrophages, cholesteryl ester transfer protein-mediated cholesteryl ester transfer, and hepatic HDL-cholesteryl ester selective uptake were evaluated. Equally, the capacity of postprandial HDL particles isolated from patients before and after ERN/LRPT treatment to mediate RCT to feces was evaluated in vivo in human apolipoprotein B/cholesteryl ester transfer protein double transgenic mouse model. Compared with baseline, ERN/LRPT significantly reduced postprandial hypertriglyceridemia (incremental area under the curve-triglyceride: -53%; P=0.02). Postprandial increase in endogenous plasma cholesteryl ester transfer protein activity was completely abolished after ERN/LRPT treatment. Despite a slight reduction in plasma cholesterol efflux capacity from human THP-1 macrophages, evaluation of global RCT efficacy by combining both ex vivo and in vivo approaches indicate that postprandial HDL particles formed under ERN/LRPT therapy displayed a greater capacity for HDL-mediated RCT to feces.
  
  
  CONCLUSIONS
  ERN/LRPT treatment efficiently attenuates atherogenic postprandial lipemia and stimulates HDL-mediated cholesterol return to the liver and elimination into feces during postprandial phase, thus maintaining an efficient removal of cholesterol from the body.
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.).
authors.forename: Petra
authors.initials: P
authors.lastname: El Khoury
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.).
authors.forename: Elisa
authors.initials: E
authors.lastname: Waldmann
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.).
authors.forename: Thierry
authors.initials: T
authors.lastname: Huby
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.).
authors.forename: Julie
authors.initials: J
authors.lastname: Gall
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.).
authors.forename: Philippe
authors.initials: P
authors.lastname: Couvert
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.).
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lacorte
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.).
authors.forename: John
authors.initials: J
authors.lastname: Chapman
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.).
authors.forename: Eric
authors.initials: E
authors.lastname: Frisdal
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.).
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesnik
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.).
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Parhofer
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.).
authors.forename: Wilfried
authors.initials: W
authors.lastname: Le Goff
authors.affiliation: From the INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMRS-1166 Hôpital de la Pitié, Paris, France (P.E.K., T.H., J.G., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University Saint-Joseph, Beyrouth, Lebanon (P.E.K.); ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France (T.H., P.C., J.-M.L., E.F., P.L., W.L.G., M.G.); University of Munich, Munich, Germany (E.W., K.G.P.); and INSERM, Emeritus Research Director (J.C.). maryse.guerin@upmc.fr.
authors.forename: Maryse
authors.initials: M
authors.lastname: Guerin
mesh_terms: D000368:Aged; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D016466:CHO Cells; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D003412:Cricetulus; D004338:Drug Combinations; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008822:Mice, Transgenic; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use*; D019518:Postprandial Period; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome
chemical_list: C569471:APOB protein, human; D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004338:Drug Combinations; D007211:Indoles; C518174:MK-0524; D009525:Niacin; D002784:Cholesterol
keywords: CETP; HDL-CE uptake; cholesterol efflux; in vivo metabolic studies; macrophage