0000000000189954

AUTHOR

Alan R. Tall

showing 3 related works from this author

Reduced VLDL clearance in ApoeNpc1 mice is associated with increased Pcsk9 and Idol expression and decreased hepatic LDL-receptor levels

2010

Niemann-Pick type C1 (NPC1) promotes the transport of LDL receptor (LDL-R)-derived cholesterol from late endosomes/lysosomes to other cellular compartments. NPC1-deficient cells showed impaired regulation of liver_X receptor (LXR) and sterol regulatory element-binding protein (SREBP) target genes. We observed that Apoe(-/-)Npc1(-/-) mice displayed a marked increase in total plasma cholesterol mainly due to increased VLDL, reflecting decreased clearance. Although nuclear SREBP-2 and Ldlr mRNA levels were increased in Apoe(-/-)Npc1(-/-) liver, LDL-R protein levels were decreased in association with marked induction of proprotein convertase subtilisin/kexin type 9 (Pcsk9) and inducible degrade…

Apolipoprotein EreceptorCholesterol VLDLLDL/metabolismMacrophages Peritoneal/cytologyBiochemistryMiceEndocrinologyhemic and lymphatic diseasesReceptorsOrphan Nuclear Receptors/geneticspolycyclic compoundsnuclear receptorCells CulturedResearch ArticlesLiver X ReceptorsMice KnockoutCulturedSterol Regulatory Element Binding Protein 2/geneticslipoproteinSerine EndopeptidasesIntracellular Signaling Peptides and ProteinsLamin Type AOrphan Nuclear ReceptorsTriglycerides/bloodCholesterolLiverProteins/geneticsKexinlipids (amino acids peptides and proteins)Proprotein ConvertasesProprotein Convertase 9Sterol Regulatory Element Binding Protein 1Niemann-Pick diseaseSterol Regulatory Element Binding Protein 2medicine.medical_specialtyCellsKnockoutUbiquitin-Protein LigasesReceptors LDL/metabolismSerine Endopeptidases/geneticsQD415-436BiologyCholesterol/blooddigestive systemApolipoproteins ELiver/physiologySterol Regulatory Element Binding Protein 1/geneticsNiemann-Pick C1 ProteinInternal medicinemedicineAnimalsPeritoneal/cytologyCholesterol VLDL/metabolismUbiquitin-Protein Ligases/geneticsLiver X receptorTriglyceridesMacrophagesPCSK9Proteinsnutritional and metabolic diseasesVLDL/metabolismLamin Type A/metabolismCell BiologySterol regulatory element-binding proteinEndocrinologyReceptors LDLLDL receptorMacrophages PeritonealSterol regulatory element-binding protein 2atherosclerosisApolipoproteins E/geneticsLipoproteinJournal of Lipid Research
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The role of plasma lipid transfer proteins in lipoprotein metabolism and atherogenesis.

2008

The plasma lipid transfer proteins promote the exchange of neutral lipids and phospholipids between the plasma lipoproteins. Cholesteryl ester transfer protein (CETP) facilitates the removal of cholesteryl esters from HDL and thus reduces HDL levels, while phospholipid transfer protein (PLTP) promotes the transfer of phospholipids from triglyceride-rich lipoproteins into HDL and increases HDL levels. Studies in transgenic mouse models and in humans with rare genetic deficiencies (CETP) or common genetic variants (CETP and PLTP) highlight the central role of these molecules in regulating HDL levels. Human CETP deficiency is associated with dramatic elevations of HDL cholesterol and apolipopr…

Genetically modified mousemedicine.medical_specialtyApolipoprotein BLipoproteinscholesteryl ester transfer proteinQD415-436BiochemistryLipoprotein Metabolismchemistry.chemical_compoundEndocrinologyPhospholipid transfer proteinInternal medicineCholesterylester transfer proteinmedicineAnimalsHumansCETP inhibitorPhospholipidsPolymorphism GeneticbiologyChemistryCholesterolTorcetrapibCell BiologyAtherosclerosisphospholipid transfer proteincarbohydrates (lipids)EndocrinologyBiochemistrylow density lipoproteinsToxicitybiology.proteinlipids (amino acids peptides and proteins)high density lipoproteinsCarrier ProteinsJournal of lipid research
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CAMKIIγ suppresses an efferocytosis pathway in macrophages and promotes atherosclerotic plaque necrosis

2017

Atherosclerosis is the underlying etiology of cardiovascular disease, the leading cause of death worldwide. Atherosclerosis is a heterogeneous disease in which only a small fraction of lesions lead to heart attack, stroke, or sudden cardiac death. A distinct type of plaque containing large necrotic cores with thin fibrous caps often precipitates these acute events. Here, we show that Ca2+/calmodulin-dependent protein kinase gamma (CaMKII gamma) in macrophages plays a major role in the development of necrotic, thin-capped plaques. Macrophages in necrotic and symptomatic atherosclerotic plaques in humans as well as advanced atherosclerotic lesions in mice demonstrated activation of CaMKII. We…

0301 basic medicineMalePathologymedicine.medical_specialtyPhagocytosisGene ExpressionInflammationApoptosisMice TransgenicBiologyPHAGOCYTOSISLIPID MEDIATORS03 medical and health sciencesNecrosisENDOPLASMIC-RETICULUM STRESSINFLAMMATIONCa2+/calmodulin-dependent protein kinaseC/EBP HOMOLOGOUS PROTEINmedicineMacrophageAnimalsHumansKINASE-IILiver X receptorEfferocytosisCells CulturedLiver X ReceptorsAPOE-DEFICIENT MICEc-Mer Tyrosine KinaseATF6MacrophagesAPOPTOTIC CELL ACCUMULATIONGeneral MedicineMERTKAtherosclerosisPlaque AtheroscleroticActivating Transcription Factor 6Enzyme ActivationMice Inbred C57BL030104 developmental biologyRESOLUTIONmedicine.symptomCalcium-Calmodulin-Dependent Protein Kinase Type 2LIVER-X-RECEPTORResearch ArticleSignal TransductionJournal of Clinical Investigation
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