Genomes and Genes
- Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1cPhilippe Costet
INSERM, U539, CHU Hotel Dieu, 44000, Nantes, France
J Biol Chem 281:6211-8. 2006..Together, these results show that PCSK9 expression is regulated by nutritional status and insulinemia...
- Elevated plasma PCSK9 level is equally detrimental for patients with nonfamilial hypercholesterolemia and heterozygous familial hypercholesterolemia, irrespective of low-density lipoprotein receptor defectsGilles Lambert
Faculte de Medecine, Universite de Nantes, UMR Phan 1280, Nantes, France Lipid Research Group, Heart Research Institute, Sydney, Australia Electronic address
J Am Coll Cardiol 63:2365-73. 2014..convertase subtilisin/kexin type 9 (PCSK9) levels constitute an even greater risk for patients who already have reduced low-density lipoprotein receptor (LDLR) levels, such as those with heterozygous familial hypercholesterolemia (HeFH)?..
- Fasting induces hyperlipidemia in mice overexpressing proprotein convertase subtilisin kexin type 9: lack of modulation of very-low-density lipoprotein hepatic output by the low-density lipoprotein receptorGilles Lambert
Universite de Nantes, UFR de Medecine, Institut National de la Sante et de la Recherche Medicale, Unité 539, Centre Hospitalier Universitaire Hotel Dieu, 44093 Nantes, France
Endocrinology 147:4985-95. 2006..In summary, the negative modulation of LDLr expression by PCSK9, which decreases plasma LDL clearance, also promotes an overproduction of nascent VLDL in vivo upon fasting...
- PCSK9: a promising therapeutic target for dyslipidemias?Gilles Lambert
University of Nantes, Medical School, INSERM U539, CHU Hotel Dieu, 3 e Nord, 1 Place Alexis Ricordeau, F 44093 Nantes cedex 1, France
Trends Endocrinol Metab 17:79-81. 2006..humans, the characterization of PCSK9-deficient mice hypersensitive to statins and the severely pathological phenotype of D374Y PCSK9-mutated patients shed a new light on this gene: is it a promising therapeutic target for dyslipidemias?..
- Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cellsFlorent Lalanne
Institut National de la Santé et de la Recherche Médicale U539, Centre Hospitalier Universitaire, Hotel Dieu, Nantes, France
J Lipid Res 46:1312-9. 2005..Finally, we show that unlike PCSK9 overexpression in mice, the S127R mutation in patients led to increased VLDL apoB levels, suggesting a potential gain of function for S127R-PCSK9 in humans...
- Unravelling the functional significance of PCSK9Gilles Lambert
Universite de Nantes, INSERM U539, CHU Hotel Dieu, Nantes, France
Curr Opin Lipidol 18:304-9. 2007..This review summarizes recent studies published in print or online before January 2007 which have investigated the functional significance of this intriguing protease...
- The 5A apolipoprotein A-I mimetic peptide displays antiinflammatory and antioxidant properties in vivo and in vitroFatiha Tabet
Lipid Research Group, Heart Research Institute, Sydney, New South Wales, Australia
Arterioscler Thromb Vasc Biol 30:246-52. 2010..The effects of the 5A/PLPC complex were no longer apparent in HCAECs knocked down for ABCA1...
- The PCSK9 decadeGilles Lambert
Laboratoire Inserm U957, Universite de Nantes, Faculte de Medecine, Nantes, France
J Lipid Res 53:2515-24. 2012..Initial data from investigations of PCSK9 inhibition in humans are promising and indicate that PCSK9 inhibition may be a viable new therapeutic option for the treatment of dyslipidemia and associated cardiovascular diseases...
- The differential apoA-I enrichment of prebeta1 and alphaHDL is detectable by gel filtration separationMaud Chetiveaux
INSERM U539, Centre de Recherche en Nutrition Humaine, CHU Hotel Dieu, Nantes, France
J Lipid Res 43:1986-93. 2002..This original and new method should help to understand the kinetics of HDL in humans and the reverse cholesterol transport dynamics...
- Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicityGrace L Guo
Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 278:45062-71. 2003..Furthermore, FXR, PXR, and CAR protect against hepatic bile acid toxicity in a complementary manner, suggesting that they serve as redundant but distinct layers of defense to prevent overt hepatic damage by bile acids during cholestasis...
- The farnesoid X-receptor is an essential regulator of cholesterol homeostasisGilles Lambert
Molecular Disease Branch, NHLBI, National Institutes of Health NIH, Bethesda, Maryland 20892, USA
J Biol Chem 278:2563-70. 2003..These data demonstrate that FXR is a critical regulator of normal cholesterol metabolism and that genetic changes affecting FXR function have the potential to be pro-atherogenic...
- Loss of functional farnesoid X receptor increases atherosclerotic lesions in apolipoprotein E-deficient miceElyisha A Hanniman
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
J Lipid Res 46:2595-604. 2005..In conclusion, loss of FXR function is associated with decreased survival, increased severity of defects in lipid metabolism, and more extensive aortic plaque formation in a mouse model of atherosclerotic disease...
- Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypesKimihiko Matsusue
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Frederick, Maryland 20892, USA
J Clin Invest 111:737-47. 2003..These data indicate that hepatic PPARgamma plays a critical role in the regulation of TG content and in the homeostasis of blood glucose and insulin resistance in steatotic diabetic mice...
- [PCSK9: a new gene involved in familial hypercholesteremia]Gilles Lambert
Med Sci (Paris) 20:1068-70. 2004
- Hepatic CCAAT/enhancer binding protein alpha mediates induction of lipogenesis and regulation of glucose homeostasis in leptin-deficient miceKimihiko Matsusue
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Mol Endocrinol 18:2751-64. 2004..Taken together, these results indicate that hepatic C/EBP alpha plays a critical role in the acceleration of lipogenesis in ob/ob mice and in glucose homeostasis by the indirect regulation of insulin secretion...
- Disruption of hepatic C/EBPalpha results in impaired glucose tolerance and age-dependent hepatosteatosisYusuke Inoue
Laboratory of Metabolism, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 279:44740-8. 2004..These data demonstrate that hepatic C/EBPalpha is critical for ammonia detoxification and glucose and lipid homeostasis in adult mice...
- Peroxisome proliferator-activated receptor beta/delta regulates very low density lipoprotein production and catabolism in mice on a Western dietTaro E Akiyama
Laboratory of Metabolism, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 37, Bethesda, MD 20892, USA
J Biol Chem 279:20874-81. 2004....
- Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South AfricaVivienne M Homer
Canterbury Health Laboratories, 8001 Christchurch, New Zealand
Atherosclerosis 196:659-66. 2008..Our study therefore indicates that PCSK9 mediated inhibition of the LDLR does not require PCSK9 autocatalytic cleavage or secretion, suggesting that PCSK9 may also function intracellularly...
- Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatmentGilles Lambert
The Heart Research Institute, Sydney, Australia
Clin Chem 54:1038-45. 2008..Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment...
- Hepatocyte nuclear factor 4alpha in the intestinal epithelial cells protects against inflammatory bowel diseaseSung Hoon Ahn
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Inflamm Bowel Dis 14:908-20. 2008..While HNF4alpha expression is critical for liver function, its role in the gut and in the pathogenesis of inflammatory bowel disease (IBD) is unknown...
- Disruption of the Arnt gene in endothelial cells causes hepatic vascular defects and partial embryonic lethality in miceSun Hee Yim
Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA
Hepatology 44:550-60. 2006..Adult ArntDeltaEC mice carrying embryonic hepatic defects developed what was possibly an early stage of cirrhosis with consequences of limited oxygen availability and altered lipid metabolism...
- Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4 alpha, and PGC-1 alphaElyhisha A Hanniman
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
J Lipid Res 47:2503-14. 2006..Together, these results indicate that the induction of apoA-IV expression in fasting and diabetes likely involves PGC-1 alpha-mediated coactivation of HNF-4 alpha in addition to glucocorticoid-dependent actions...
- Conditional disruption of the peroxisome proliferator-activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol effluxTaro E Akiyama
Laboratory of Metabolism, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Mol Cell Biol 22:2607-19. 2002..Together, these data indicate that PPAR gamma plays a critical role in the regulation of cholesterol homeostasis by controlling the expression of a network of genes that mediate cholesterol efflux from cells and its transport in plasma...
- The ATP binding cassette transporter A1 (ABCA1) modulates the development of aortic atherosclerosis in C57BL/6 and apoE-knockout miceCharles W Joyce
Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 99:407-12. 2002....