Affinage

APOC3

Apolipoprotein C-III · UniProt P02656

Length
99 aa
Mass
10.9 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ApoC-III is a secreted apolipoprotein that raises plasma triglycerides by inhibiting the hepatic clearance of triglyceride-rich lipoprotein (TRL) remnants via the LDLR/LRP1 receptor axis and, in the absence of apoE-mediated clearance pathways, by suppressing lipoprotein lipase (LPL) activity in adipose tissue (PMID:27400128, PMID:31092690). ApoC-III competitively displaces apoE from the VLDL surface, reducing receptor-mediated uptake; genetic restoration of apoE normalizes the hypertriglyceridemic phenotype of apoC-III-overexpressing mice (PMID:8864964). Intracellularly, apoC-III promotes second-step VLDL1 assembly in the hepatic microsomal lumen through its C-terminal lipid-binding domain (Lys58) and N-terminal region, with mutations at either site impairing VLDL maturation and TAG secretion (PMID:20097930, PMID:21676879). Transcription of APOC3 is positively driven by HNF-4, Foxo1, SP1, PGC-1β/ERRα, SMAD3/4, and ATF-2, and repressed by insulin (via Foxo1 nuclear exclusion), MAP kinase signaling (via HNF-4 suppression), Rev-erbα, and Jun family members, with a distal enhancer hormone response element essential for both hepatic and intestinal expression in vivo (PMID:15546000, PMID:10551874, PMID:12454280, PMID:10995777, PMID:10893424).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1987 High

    Identification of Thr74 as the O-glycosylation site of apoC-III established that a single nucleotide change (Thr74→Ala) abolishes glycosylation, explaining the apoC-III-0 isoform.

    Evidence Molecular cloning and DNA sequencing of APOC3 gene from a subject with elevated apoC-III-0

    PMID:3123586

    Open questions at the time
    • Functional consequence of glycosylation for lipoprotein metabolism was unknown
    • No assessment of secretion or lipid binding of the unglycosylated form
  2. 1988 High

    Site-directed mutagenesis showed that O-glycosylation at Thr74 is dispensable for apoC-III secretion and lipoprotein binding, ruling out glycosylation as a requirement for core apoC-III function.

    Evidence Thr74→Ala mutagenesis in stably transfected C127 cells with pulse-chase and density gradient ultracentrifugation

    PMID:3192519

    Open questions at the time
    • Whether glycoforms differ in receptor-mediated clearance was not tested
    • In vivo relevance not assessed
  3. 1989 High

    Mapping of a 13-nucleotide hepatic-specific promoter element (C3P) and its cognate nuclear factor AF-1 established that APOC3 transcription is controlled by tissue-specific trans-acting factors.

    Evidence Promoter deletion/mutation analysis with transient transfection and nuclear extract binding assays in hepatic vs. non-hepatic cells

    PMID:2777781

    Open questions at the time
    • Identity of AF-1 protein was unknown
    • Intestinal regulatory elements not mapped
  4. 1990 High

    Systematic promoter dissection revealed distinct upstream regions controlling hepatic vs. intestinal transcription and identified mutually exclusive factors (CIIIB1 repressor, CIIIB2 activator) at a proximal element, establishing combinatorial regulation of APOC3.

    Evidence Promoter deletion, DNase I footprinting, and methylation interference with rat liver nuclear extracts in HepG2 and Caco-2 cells

    PMID:2161843

    Open questions at the time
    • Molecular identity of CIIIB1 and CIIIB2 not determined
    • In vivo relevance of these elements not tested
  5. 1992 High

    Two converging discoveries established the primary mechanism of apoC-III-driven hypertriglyceridemia: transgenic overexpression showed apoC-III reduces VLDL fractional catabolic rate by altering the apoC-III/apoE ratio on particles, and HNF-4 was identified as the activating transcription factor at the proximal CIIIB element opposed by orphan receptor repressors.

    Evidence Radiolabeled VLDL turnover in transgenic mice plus EMSA and cotransfection in HepG2 cells with affinity measurements

    PMID:1430212 PMID:1639815

    Open questions at the time
    • Which hepatic receptors mediate apoC-III-sensitive clearance was unknown
    • Whether apoC-III directly inhibits LPL in vivo was unresolved
  6. 1994 High

    Insulin was shown to transcriptionally suppress APOC3 via a mechanism later attributed to Foxo1, and an NF-κB element was identified in the promoter conferring cytokine-inducible regulation, revealing hormonal and inflammatory control layers.

    Evidence Nuclear run-on assays in streptozotocin-diabetic mice, HepG2 reporter transfections, EMSA with purified NF-κB and antibody supershift

    PMID:7868970 PMID:8036173

    Open questions at the time
    • Insulin-responsive cis-element and trans-factor not yet identified
    • Physiological relevance of NF-κB-mediated regulation in vivo untested
  7. 1995 High

    The distal enhancer was shown to function through SP1 sites cooperating with HNF-4 at the proximal promoter, defining a long-range transcriptional activation mechanism for APOC3.

    Evidence DNA binding, competition, and supershift assays with cotransfection in HepG2 cells

    PMID:7640286

    Open questions at the time
    • In vivo role of SP1 sites not confirmed
    • Chromatin architecture of enhancer-promoter communication unknown
  8. 1996 High

    Crossbreeding apoC-III and apoE transgenic mice normalized hypertriglyceridemia, proving that apoC-III raises TG by competitively displacing apoE from the lipoprotein surface and thereby reducing receptor binding.

    Evidence Transgenic mouse crossbreeding, fibroblast receptor binding assays, heparin-Sepharose binding, vitamin A fat tolerance test

    PMID:8864964

    Open questions at the time
    • Which specific receptors are inhibited by apoC-III was not defined
    • Stoichiometry of apoC-III/apoE displacement not quantified
  9. 1998 High

    ATF-2 was identified as a positive regulator of APOC3 that counteracts Jun-mediated repression, adding stress-responsive signaling to the transcriptional control network.

    Evidence DNase I footprinting, cotransfection in HepG2 cells, promoter mutation analysis

    PMID:9760243

    Open questions at the time
    • Physiological stimuli activating ATF-2 at the APOC3 promoter not identified
    • In vivo validation lacking
  10. 1999 High

    MAP kinase signaling was shown to repress APOC3 transcription by reducing HNF-4 levels, and nuclear receptor heterodimers (RXRα/RARα, RXRα/T3Rβ, PPARα) were mapped to specific DR-motifs, integrating metabolic and hormonal signals at defined cis-elements.

    Evidence MEK inhibitor and phorbol ester treatments in HepG2 cells with promoter mapping; DNA binding, methylation interference, and cotransfection with ligands

    PMID:10551874 PMID:9893992

    Open questions at the time
    • In vivo contribution of individual nuclear receptors to APOC3 regulation not established
    • Cross-talk between MAP kinase and nuclear receptor pathways not tested
  11. 2000 High

    SMAD3/4 were shown to transactivate APOC3 through physical interaction with HNF-4, and in vivo transgenic studies confirmed that the enhancer hormone response element and SP1 sites are essential for all detectable APOC3 expression, integrating TGF-β signaling and consolidating the enhancer architecture.

    Evidence Co-IP, GST pull-down, antisense ribozyme knockdown of HNF-4 in HepG2 cells; transgenic mice with enhancer mutations

    PMID:10893424 PMID:10995777 PMID:11121483

    Open questions at the time
    • Pathophysiological context for TGF-β regulation of APOC3 undefined
    • Whether SMAD signaling is active at the endogenous APOC3 locus not shown
  12. 2002 High

    Rev-erbα was established as a physiological repressor of APOC3 through a response element downstream of the TATA box, with knockout mice showing elevated apoC-III and VLDL-TG, linking circadian clock components to triglyceride homeostasis.

    Evidence Cotransfection in rat hepatocytes, promoter mutation and gel-shift assays, Rev-erbα knockout mouse phenotyping

    PMID:12454280

    Open questions at the time
    • Whether circadian oscillation of apoC-III drives diurnal TG variation not tested
    • Interaction with other clock components at the APOC3 promoter unknown
  13. 2004 High

    Foxo1 was identified as the transcription factor mediating insulin suppression of APOC3: insulin phosphorylates and excludes Foxo1 from the nucleus, and constitutively active Foxo1 causes hypertriglyceridemia, mechanistically connecting insulin resistance to elevated apoC-III.

    Evidence Adenoviral Foxo1 overexpression in mouse liver, promoter mutagenesis, constitutively active Foxo1 transgenic and diabetic (NOD, db/db) mouse models

    PMID:15546000

    Open questions at the time
    • Whether other insulin-regulated factors contribute to APOC3 suppression not excluded
    • Post-translational regulation of apoC-III by insulin not addressed
  14. 2005 High

    Genetic epistasis showed that apoC-III deficiency rescues apoE-overexpression-induced hyperlipidemia by restoring LPL-mediated TG hydrolysis, establishing that apoC-III is a more potent LPL inhibitor than apoE in vivo.

    Evidence Adenoviral apoE4 overexpression in Apoc3+/- and Apoc3-/- mice, LPL activity assays, in vivo adipose fatty acid uptake

    PMID:15863838

    Open questions at the time
    • Whether apoC-III inhibits LPL by direct binding or by substrate shielding not distinguished
    • Tissue-specific LPL regulation by apoC-III not fully mapped
  15. 2010 High

    Two complementary studies revealed apoC-III's intracellular role in VLDL assembly: PGC-1β/ERRα was identified as an upstream transcriptional driver with liver-specific APOC3 knockdown rescuing PGC-1β-induced hypertriglyceridemia, and the Ala23Thr variant was shown to impair second-step VLDL1 maturation by preventing lipid droplet-VLDL precursor fusion in the ER lumen.

    Evidence Adenoviral knockdown in mouse liver with proteomic complex identification; metabolic labeling in McA-RH7777 cells with density gradient ultracentrifugation and brefeldin A comparison

    PMID:20097930 PMID:20889132

    Open questions at the time
    • Structural basis for N-terminal involvement in VLDL assembly unknown
    • Whether intracellular apoC-III role is physiologically rate-limiting in normal livers not established
  16. 2011 High

    Charge-swap mutagenesis at Lys58 demonstrated that the C-terminal positive charge is essential for lipid binding and TAG secretion, defining the molecular basis of apoC-III's lipid association.

    Evidence K58E/K58R mutagenesis in McA-RH7777 cells and adenoviral delivery in apoc3-null mice, Fat Western lipid-protein overlay assay

    PMID:21676879

    Open questions at the time
    • Full structural model of apoC-III on lipid surfaces lacking
    • Whether Lys58 also affects receptor-mediated clearance not tested
  17. 2016 High

    Genetic epistasis across multiple receptor-knockout backgrounds pinpointed LDLR and LRP1 as the hepatic receptors through which apoC-III inhibits TRL clearance: apoC-III ASO failed to lower TG only in LDLR/LRP1 double-knockout mice.

    Evidence ApoC-III ASO treatment in LPL-null, HSPG-null, LDLR-null, LRP1-null, and LDLR/LRP1 double-null mouse models with postprandial clearance studies

    PMID:27400128

    Open questions at the time
    • Mechanism by which apoC-III blocks LDLR/LRP1 recognition at the molecular level unknown
    • Whether apoC-III directly binds these receptors not shown
  18. 2017 High

    The APOC3 A43T variant was shown to reduce circulating apoC-III by impairing lipoprotein binding and accelerating renal catabolism, and a monoclonal antibody targeting lipoprotein-bound apoC-III phenocopied this clearance-accelerating effect.

    Evidence Human heterozygote carrier characterization, humanized mouse models, in vivo TRL clearance studies, monoclonal antibody administration

    PMID:28825717

    Open questions at the time
    • Structural basis of impaired lipoprotein binding by A43T not defined
    • Long-term efficacy and safety of antibody-mediated apoC-III removal unknown
  19. 2019 High

    Multiple studies in 2019 resolved context-dependent mechanisms: apoC-III inhibits LPL in adipose tissue specifically when apoE-mediated receptor clearance is absent; glycoforms are differentially cleared by HSPG (apoC-III2) vs. LDLR/LRP1 (apoC-III1); human APOC3 LOF carriers show accelerated VLDL-TG fractional clearance without altered production; and intestinal apoC-III modulates chylomicron size and enterocyte lipid handling.

    Evidence Compound knockout mice (Apoe-/-/Ndst1-/-) with LPL assays; TRL injection in HSPG-null and LDLR/LRP1-null mice with MS glycoform quantification; stable isotope kinetic studies in human R19X carriers; primary enteroid cultures

    PMID:28159868 PMID:30580564 PMID:31092690 PMID:31152000 PMID:31390883

    Open questions at the time
    • Why different glycoforms are preferentially cleared by different receptors is mechanistically unexplained
    • Intestinal apoC-III contribution to systemic TG regulation relative to hepatic apoC-III not quantified
  20. 2021 Medium

    Post-translational guanidinylation of apoC-III in CKD was identified as a modification that augments its pro-inflammatory effects on monocytes and promotes renal fibrosis, extending apoC-III biology beyond lipoprotein metabolism.

    Evidence Mass spectrometry of CKD patient samples, monocyte stimulation, unilateral ureter ligation and vascular injury models in humanized mice

    PMID:34588185

    Open questions at the time
    • Whether guanidinylation affects apoC-III lipoprotein binding or clearance not tested
    • Stoichiometry and prevalence of guanidinylation across CKD stages unknown
    • Independent replication needed
  21. 2022 High

    Comprehensive postprandial kinetic studies in human APOC3 LOF carriers confirmed that reduced apoC-III accelerates both TRL lipolysis and remnant removal without affecting lipoprotein production rates, providing definitive human evidence for the clearance-based mechanism.

    Evidence Stable isotope kinetic studies of apoB48 and apoB100 across chylomicron, VLDL1, VLDL2, IDL, and LDL fractions in LOF carriers vs. controls

    PMID:36040803

    Open questions at the time
    • Relative contribution of LPL enhancement vs. receptor-mediated clearance to the net effect in humans not partitioned
    • Whether findings generalize to pharmacological apoC-III reduction in non-carriers requires validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of how apoC-III on the lipoprotein surface sterically or conformationally blocks LDLR/LRP1 recognition, and the molecular determinants governing glycoform-specific receptor preference, remain unresolved.
  • No high-resolution structural model of apoC-III on lipoprotein particles
  • Molecular mechanism of receptor occlusion not defined
  • Glycoform-receptor selectivity mechanism unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0008289 lipid binding 3
Localization
GO:0005576 extracellular region 5 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-74160 Gene expression (Transcription) 9 R-HSA-1430728 Metabolism 7 R-HSA-162582 Signal Transduction 4
Partners
APOEFOXO1HNF4ANR1D1PPARGC1BSMAD3SMAD4SP1

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 ApoC-III overexpression in transgenic mice causes hypertriglyceridemia primarily by decreasing the fractional catabolic rate of VLDL particles, due to increased apoC-III and decreased apoE content on VLDL, leading to impaired hepatic receptor-mediated uptake rather than reduced lipoprotein lipase activity or substrate quality. Human apoC-III transgenic mouse lines, radiolabeled VLDL turnover studies, in vitro LPL assays, hepatoma cell uptake assays, primary hepatocyte secretion studies The Journal of clinical investigation High 1430212
1996 ApoC-III on VLDL competitively displaces apoE, reducing lipoprotein receptor binding and heparin-sulfate proteoglycan interaction; addition of exogenous apoE rescues receptor binding, and crossbreeding apoC-III transgenic mice with apoE transgenic mice normalizes hypertriglyceridemia, demonstrating a functionally significant reciprocal relationship between apoC-III and apoE on triglyceride-rich lipoproteins. Transgenic mouse crossbreeding, fibroblast lipoprotein receptor binding assays, heparin-Sepharose binding assays, vitamin A fat tolerance test Journal of lipid research High 8864964
1989 A 13-nucleotide element (C3P) in the apoCIII promoter is required for high-level hepatic expression and is sufficient to confer hepatic-specific expression to a heterologous promoter; a hepatic nuclear protein (AF-1) binds this element, and qualitative differences in C3P-binding proteins across cell types account for tissue-specific activity. Promoter deletion/mutation analysis, transient transfection in hepatic vs. non-hepatic cells, nuclear extract binding assays The Journal of biological chemistry High 2777781
1990 The region -890 to -686 of the apoCIII promoter contains nuclear factor binding sites required for both hepatic and intestinal transcription; the region -686 to -553 is recognized by factors promoting only hepatic transcription; a proximal element (-86 to -74) is bound by two mutually exclusive factors (CIIIB1 suppressing transcription and CIIIB2 associated with normal transcription). Promoter deletion analysis, nucleotide substitution, DNase I footprinting with rat liver nuclear extracts, DNA binding and methylation interference assays, transient transfection in HepG2 and Caco-2 cells The Journal of biological chemistry High 2161843
1992 HNF-4 activates APOC3 gene transcription by binding the CIIIB element (-87 to -63) of the proximal promoter, while ARP-1, EAR-2, and EAR-3 repress this same element; HNF-4 can reverse ARP-1-mediated repression, and the opposing effects result from competition for binding to the same regulatory element. Transcriptional activation by HNF-4 requires synergistic interaction with factors at upstream elements. Electrophoretic mobility shift assays, dissociation constant measurements, cotransfection experiments in HepG2 cells, promoter mutation analysis The Journal of biological chemistry High 1639815
1994 Insulin transcriptionally down-regulates apoC-III gene expression; in streptozotocin-diabetic mice, apoC-III mRNA increases 1.4-1.5-fold and returns to normal with insulin treatment; nuclear run-on assays confirm this is a transcriptional effect; dose-dependent insulin suppression of apoC-III promoter activity is demonstrated in HepG2 transfection experiments. Streptozotocin mouse model, Northern blot, RNase protection assay, nuclear run-on transcription assay, HepG2 transfection with apoC-III reporter construct Journal of lipid research High 7868970
1994 An NF-κB binding element located ~150 bp upstream of the apoCIII transcription start site binds NF-κB p50/p65 subunits; this element confers PMA- and IL-1β-inducible transcriptional activity to a heterologous promoter in HepG2 cells, but its inducible activity is suppressed by a distal apoCIII enhancer element ~500 bp upstream. Electrophoretic mobility shift assay with purified NF-κB and HepG2 nuclear extracts, antibody supershift with p50/p65 antibodies, transient transfection of heterologous promoter-reporter constructs in HepG2 cells Nucleic acids research High 8036173
1995 The apoCIII distal enhancer contains multiple SP1 binding sites (elements F, H, I) and a specialized hormone response element (element G) recognized by ARP-1/EAR-3 but not HNF-4; SP1 and HNF-4 cooperate to achieve 10-fold enhancement of the proximal promoter; transcriptional activation requires an intact hormone response element on the proximal promoter. DNA binding assays, competition assays, supershift assays, transient transfection in HepG2 cells, promoter deletion and mutation analysis Biochemistry High 7640286
1999 The MAP kinase signaling pathway regulates apoCIII transcription: inhibition of MEK increases apoCIII transcriptional activity 5-8-fold while activation decreases it 3-5-fold. The MAP kinase-responsive element maps to -740 in the apoCIII promoter and the major protein binding this site is HNF-4; MAP kinase inhibition increases HNF-4 mRNA and protein levels, indicating that MAP kinase controls apoCIII via regulation of HNF-4 expression. PD98059 MEK inhibitor and phorbol ester treatment of HepG2 cells, transient transfection with apoCIII promoter-reporter constructs, promoter deletion mapping, protein binding assays, HNF-4 mRNA and protein quantification The Journal of biological chemistry High 10551874
1999 Ligand-dependent nuclear receptors RXRα/RARα, RXRα/T3Rβ, and PPARα bind apoCIII promoter hormone response elements; RXRα/RARα heterodimers increase apoCIII promoter activity ~2-fold with retinoid ligands while RXRα/T3Rβ represses it in the presence of T3. Different DR-motifs on elements B (DR-1), G (DR-5), and I4 (DR-1) are specifically recognized by distinct receptor combinations. DNA binding assays, methylation interference experiments, cotransfection in HepG2 cells with ligand treatment, promoter mutation analysis Biochemistry High 9893992
1998 ATF-2 binds three regions of the apoCIII promoter and transactivates it ~1.6-fold; Jun family members (c-Jun, JunB, JunD) repress apoCIII transcription by interfering with the distal enhancer; ATF-2 and HNF-4 have additive positive effects on apoCIII transcription, and ATF-2 can counteract Jun-mediated repression. DNase I footprinting, cotransfection in HepG2 cells, promoter mutation analysis, synthetic promoter constructs Biochemistry High 9760243
2000 SMAD3 and SMAD3-SMAD4 transactivate the apoCIII promoter 15-70-fold requiring an intact hormone response element; SMAD proteins physically interact with HNF-4 (demonstrated by co-immunoprecipitation and GST pull-down); SMAD-mediated transactivation is abolished when HNF-4 is suppressed by antisense ribozyme, indicating TGF-β/SMAD signaling regulates apoCIII via physical and functional interaction with HNF-4. Cotransfection in HepG2 cells, dominant-negative SMAD4, antisense ribozyme knockdown of HNF-4, co-immunoprecipitation, GST pull-down assay The Journal of biological chemistry High 10995777
2000 A hormone response element in the apoCIII enhancer is essential for intestinal and renal expression of the apoA-I gene and for all detectable apoCIII gene expression in vivo; mutations in the apoCIII enhancer alone abolish intestinal apoA-I and apoCIII expression and reduce hepatic apoA-I by 80%. Transgenic mice carrying wild-type or enhancer-mutant apoA-I/apoCIII gene cluster, tissue-specific reporter (CAT) gene expression analysis The Journal of biological chemistry High 10893424
2000 SP1 binding sites in the apoCIII enhancer are required for apoCIII gene expression; mutations in three SP1 sites reduce hepatic and intestinal CAT (apoCIII reporter) expression to 4% of control and reduce hepatic and intestinal apoA-I expression to 14% of control in transgenic mice. Transgenic mice carrying wild-type or SP1-site-mutant apoA-I/apoCIII gene cluster, tissue mRNA and reporter gene analysis Nucleic acids research High 11121483
2002 Rev-erbα acts as a physiological repressor of apoC-III gene transcription by binding a Rev-erbα response element (AGGTCA half-site at -23/-18) downstream of the TATA box in the apoCIII promoter; Rev-erbα-deficient mice have elevated serum apoC-III mRNA, apoC-III protein, and VLDL triglycerides. Cotransfection in rat hepatocytes and RK13 cells, promoter deletion and mutation analysis, gel-shift experiments, Rev-erbα knockout mouse phenotype analysis Journal of lipid research High 12454280
2004 Foxo1 mediates insulin suppression of apoC-III transcription: Foxo1 binds a consensus site in the apoC-III promoter and stimulates hepatic apoC-III expression; deletion or mutation of the Foxo1 binding site abolishes insulin response; adenoviral Foxo1 overexpression in mouse liver increases apoC-III expression and causes hypertriglyceridemia; constitutively active Foxo1 transgenic mice are hypertriglyceridemic; Foxo1 is deregulated (elevated, nuclear) in diabetic mice. Adenoviral gene transfer in mice, promoter binding assays, site-directed mutagenesis of Foxo1 binding site, constitutively active Foxo1 transgenic mice, NOD and db/db diabetic mouse models The Journal of clinical investigation High 15546000
2010 PGC-1β transcriptional coactivator drives APOC3 expression through coactivating orphan nuclear receptor ERRα at the APOC3 gene cluster; liver-specific knockdown of APOC3 significantly ameliorates PGC-1β-induced hypertriglyceridemia; nicotinic acid reduces hepatic PGC-1β and APOC3 expression, and adenoviral knockdown of PGC-1β or APOC3 recapitulates nicotinic acid's hypolipidemic effect. Adenoviral knockdown in mouse liver, proteomic analysis of PGC-1β transcriptional complex, cotransfection assays, acute and chronic nicotinic acid treatment in mice Cell metabolism High 20889132
2010 The missense APOC3 variant Ala23Thr (associated with human hypotriglyceridemia) impairs VLDL1 assembly; C3AT cells fail to assemble VLDL1 and accumulate TAG in microsomal IDL/LDL-like fractions, phenocopying brefeldin A treatment; the mutant protein is present in lumenal IDL/LDL but absent from VLDL fractions, suggesting the N-terminal region of apoC-III governs the second-step VLDL1 maturation by enabling lipid droplet-VLDL precursor fusion. Metabolic labeling of transfected McA-RH7777 cells, density gradient ultracentrifugation of secreted and lumenal lipoproteins, microsomal triglyceride transfer protein activity assay, brefeldin A comparison experiment Journal of lipid research High 20097930
2011 The C-terminal lipid-binding domain of apoC-III (specifically positive charge at Lys58) is essential for apoC-III binding to lipid and for promoting TAG secretion; the K58E mutation abolishes lipid binding (demonstrated by Fat Western overlay) and abrogates apoC-III's ability to promote VLDL-TAG secretion and lumenal lipid droplet formation in hepatic cells and apoc3-null mice. Transfection of McA-RH7777 cells and adenoviral delivery in apoc3-null mice, metabolic labeling, Fat Western lipid-protein overlay assay, microsomal lumenal lipid droplet fractionation, charge-swap mutagenesis (K58E, K58R, K58E/K60E) The Journal of biological chemistry High 21676879
2016 ApoC-III inhibits clearance of triglyceride-rich lipoproteins primarily through a hepatic mechanism mediated by LDL receptor (LDLR) and LRP1; antisense oligonucleotide reduction of apoC-III lowers plasma TGs in mice lacking LPL, HSPG receptors, LDLR, or LRP1 individually, but not in mice with combined deletion of LDLR and LRP1; apoC-III ASO has no effect on VLDL secretion or tissue lipid uptake. ApoC-III ASO treatment in multiple mouse knockout models (LPL-null, HSPG-null, LDLR-null, LRP1-null, LDLR/LRP1 double-null), postprandial clearance studies, lipoprotein injection experiments The Journal of clinical investigation High 27400128
2017 The APOC3 A43T missense variant causes reduced circulating apoC-III due to impaired binding of the mutant protein to lipoproteins and accelerated renal catabolism of free apoC-III; the reduced apoC-III content in TRLs leads to accelerated TRL clearance. A monoclonal antibody targeting lipoprotein-bound apoC-III promotes its clearance and enhances TRL catabolism in vivo. Human heterozygote carriers studied, humanized mouse models expressing APOC3 A43T, in vivo TRL clearance studies, monoclonal antibody administration in mice Nature medicine High 28825717
2019 ApoC-III inhibits LPL activity in tissues when apoE-mediated TRL clearance pathways (LDLR/LRP1 axis) are absent; in mice lacking both apoE and functional syndecan-1 HSPG, apoC-III ASO lowers plasma TG by increasing LPL activity in white adipose tissue without improving hepatic TRL clearance, demonstrating that apoE determines the mode of apoC-III action (receptor-mediated clearance vs. LPL inhibition). apoC-III ASO treatment in Apoe-/-Ndst1f/fAlb-Cre+ double-knockout mice, LPL activity assay in white adipose tissue, hepatic TRL clearance studies, clinical APOE isoform subgroup analysis Journal of lipid research High 31092690
2019 ApoC-III glycoforms are differentially cleared by hepatic TRL receptors: HSPG preferentially clears disialylated apoC-III2, while LDLR/LRP1 preferentially clears monosialylated apoC-III1; in HSPG-deficient mice, relative apoC-III2 abundance increases and clearance is accelerated (t1/2=25 min vs. 55 min in WT); volanesorsen treatment correlates with increased apoC-III2/apoC-III1 ratio and decreased plasma TG. Human TRL injection into HSPG-deficient and LDLR/LRP1-double-knockout mice, mass spectrometry-based apoC-III glycoform quantification, patient plasma analysis after volanesorsen treatment Arteriosclerosis, thrombosis, and vascular biology High 31390883
1987 ApoC-III is O-glycosylated at Thr74; a naturally occurring Thr74→Ala74 mutation (single nucleotide substitution A→G) prevents O-glycosylation of apoC-III, resulting in the un-glycosylated isoform apoC-III-0 found in elevated amounts in affected subjects. Molecular cloning of apoC-III gene from a subject with elevated apoC-III-0, DNA sequence analysis, AluI restriction site diagnosis Journal of lipid research High 3123586
1988 O-linked glycosylation at Thr74 is not required for apoC-III secretion or lipid binding; site-directed mutagenesis of Thr74→Ala74 produces unglycosylated apoC-III that is secreted normally and associates with VLDL and HDL with similar affinity as wild-type apoC-III. Site-directed mutagenesis of apoC-III gene, stable cell transfection in C127 cells, pulse-chase analysis, density gradient ultracentrifugation of secreted protein The Journal of biological chemistry High 3192519
2019 Intestinal apoC-III overexpression results in secretion of smaller, less dense chylomicron particles with reduced triacylglycerol secretion from the intestine; this effect is cell-autonomous as demonstrated in primary murine enteroid cultures. Primary murine intestinal enteroid cultures, apoC-III overexpression, lipoprotein density gradient fractionation, TAG secretion quantification Journal of lipid research Medium 28159868
2019 ApoC-III on TRLs inhibits basolateral lipid substrate transport (BLST) in enterocytes; in vivo, high plasma apoC-III diverts dietary TAG from cytosolic lipid droplets toward mitochondrial fatty acid oxidation; in enteroid cultures, excess apoC-III on TRLs inhibits TAG uptake from TRLs on the basolateral surface and reduces mitochondrial respiration. ApoC-III transgenic mice, primary murine enteroids, Seahorse mitochondrial respiration assay, lipid droplet imaging, in vivo dietary fat tracing Journal of lipid research Medium 31152000
2005 ApoC-III deficiency prevents apoE overexpression-induced hyperlipidemia in a gene-dose-dependent manner by alleviating apoE-induced inhibition of VLDL-TG hydrolysis; apoC-III is a more specific inhibitor of LPL activity than apoE in vitro; Apoc3 deficiency restores LPL-mediated fatty acid uptake in white adipose tissue in the context of 10-fold increased VLDL production. Adenoviral apoE4 overexpression in Apoe-/-, Apoc3+/-, and Apoc3-/- mice, LPL activity assay with VLDL-like emulsion particles, in vivo fatty acid uptake measurement in adipose tissue Journal of lipid research High 15863838
2019 Individuals heterozygous for the APOC3 R19X null mutation have 49% lower apoC-III, lower plasma TG and VLDL-TG due to higher fractional clearance rates (not reduced production) of VLDL-TG and VLDL-apoB100; these subjects show higher conversion of VLDL remnants to LDL with little effect on direct hepatic VLDL remnant removal. Stable isotope (deuterium-labeled) kinetic studies of VLDL-TG and apoB100 in human R19X heterozygotes vs. unaffected siblings, VLDL-TG and apoB100 fractional clearance rate and production rate determination Arteriosclerosis, thrombosis, and vascular biology High 30580564
2021 ApoC-III induces calcification in primary human valvular interstitial cells via a mitochondrial dysfunction/inflammation-mediated pathway; apoC-III is enriched in calcific vs. non-calcific aortic valve tissue and colocalizes with calcific regions in the fibrosa layer. Proteomics and immunohistochemistry of human aortic valve tissues, in vitro calcification assay in primary human valvular cell cultures with apoC-III treatment, mitochondrial dysfunction/inflammation pathway analysis The Journal of biological chemistry Medium 33334888
2021 Guanidinylation of ApoC3 (gApoC3) is a post-translational modification occurring in CKD patients, induced by guanidine and urea; gApoC3 augments the pro-inflammatory effects of native ApoC3 on monocytes in vitro, promotes kidney fibrosis and impedes vascular regeneration in humanized mice. Mass spectrometry identification of guanidinylation in CKD patient samples, 2D-proteomics in CKD mouse model, in vitro monocyte stimulation, unilateral ureter ligation and vascular injury mouse models with humanized gApoC3 Journal of the American Society of Nephrology Medium 34588185
2016 ApoC-III induces endothelial dysfunction through upregulation of TNF-α, which disrupts tight junctions by increasing JAM-1 expression, promotes leukocyte and platelet exudation, and increases THP-1 monocyte adhesion to HUVECs; siRNA silencing of TNF-α or JAM-1 abrogates APOC3-induced effects. ELISA, qRT-PCR, immunofluorescence, flow cytometry, transwell assay in HUVECs, siRNA silencing of TNF-α and JAM-1 Lipids in health and disease Medium 27619170
2016 miR-424-5p directly targets the APOC3 3'UTR to suppress APOC3 expression; APOC3 activates the NF-κB signaling pathway in aortic smooth muscle cells; miR-424-5p upregulation or APOC3 silencing suppresses SMC proliferation, migration, and inflammation and promotes apoptosis through NF-κB pathway inactivation. Luciferase reporter assay confirming miR-424-5p binding to APOC3 3'UTR, gain/loss-of-function experiments in aortic smooth muscle cells, NF-κB pathway activity assays Experimental physiology Medium 31912930
2016 A 3'UTR variant (rs4225) in APOC3 creates a functional miR-4271 binding site; the T allele suppresses APOC3 translation by facilitating miR-4271 binding while the G allele does not; subjects with the GG genotype have higher plasma APOC3 levels and the T allele is associated with decreased triglycerides. APOC3 3'UTR resequencing, luciferase reporter assay with miR-4271 co-transfection, case-control association study for CHD Scientific reports Medium 27624799
2009 Incorporation of apoC-III into reconstituted HDL (rHDL) produces smaller particles with fewer apoA-I molecules, reduces LCAT activation in a dose-dependent manner, and enhances surfactant-like membrane disruption properties; rHDL with apoC-III increases MDA production in cell culture leading to increased cellular LDL uptake; cholesteryl ester transfer ability is unaffected by apoC-III content. Reconstituted HDL synthesis with defined apoA-I:apoC-III molar ratios, LCAT activity assay, CE transfer assay, DMPC lysis assay, cell culture LDL uptake with MDA measurement Molecules and cells Medium 19326075
2022 In postprandial kinetic studies in humans with APOC3 loss-of-function mutations, reduced apoC-III markedly accelerates lipolysis of TG-rich lipoproteins and increases removal of VLDL remnants without affecting production rates of chylomicron apoB48, VLDL1, VLDL2, or LDL; concentrations of VLDL1, VLDL2, and IDL particles are substantially decreased. Stable isotope kinetic studies of apoB48 and apoB100 in chylomicrons, VLDL1, VLDL2, IDL, and LDL in LOF APOC3 mutation carriers vs. non-carriers, postprandial state JCI insight High 36040803

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Loss-of-function mutations in APOC3, triglycerides, and coronary disease. The New England journal of medicine 889 24941081
2014 Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. The New England journal of medicine 780 24941082
2008 A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science (New York, N.Y.) 571 19074352
1992 Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles. The Journal of clinical investigation 428 1430212
2014 Targeting APOC3 in the familial chylomicronemia syndrome. The New England journal of medicine 396 25470695
2002 Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides. Human molecular genetics 319 12417525
1992 Transcriptional regulation of human apolipoprotein genes ApoB, ApoCIII, and ApoAII by members of the steroid hormone receptor superfamily HNF-4, ARP-1, EAR-2, and EAR-3. The Journal of biological chemistry 285 1639815
2004 Foxo1 mediates insulin action on apoC-III and triglyceride metabolism. The Journal of clinical investigation 239 15546000
2016 ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors. The Journal of clinical investigation 211 27400128
2019 N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels. European heart journal 196 31329855
2024 Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia. The New England journal of medicine 153 38804517
2002 Identification of Rev-erbalpha as a physiological repressor of apoC-III gene transcription. Journal of lipid research 151 12454280
1994 Transcriptional regulation of the apoC-III gene by insulin in diabetic mice: correlation with changes in plasma triglyceride levels. Journal of lipid research 145 7868970
2020 The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans. Frontiers in endocrinology 132 32849270
2024 Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia: The SHASTA-2 Randomized Clinical Trial. JAMA cardiology 126 38583092
2001 Association of the Sst-I polymorphism at the APOC3 gene locus with variations in lipid levels, lipoprotein subclass profiles and coronary heart disease risk: the Framingham offspring study. Atherosclerosis 103 11500189
1990 Promoter elements and factors required for hepatic and intestinal transcription of the human ApoCIII gene. The Journal of biological chemistry 95 2161843
2017 A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels. Nature medicine 93 28825717
2004 ApoC-I and ApoC-III as potential plasmatic markers to distinguish between ischemic and hemorrhagic stroke. Proteomics 92 15274118
1992 Polymorphisms in the apolipoprotein (apo) AI-CIII-AIV gene cluster: detection of genetic variation determining plasma apo AI, apo CIII and apo AIV concentrations. Human genetics 92 1740321
2011 Missense mutation in APOC3 within the C-terminal lipid binding domain of human ApoC-III results in impaired assembly and secretion of triacylglycerol-rich very low density lipoproteins: evidence that ApoC-III plays a major role in the formation of lipid precursors within the microsomal lumen. The Journal of biological chemistry 90 21676879
1991 Variation at the apo AI/CIII/AIV gene complex is associated with elevated plasma levels of apo CIII. Atherosclerosis 89 1906714
1996 Further characterization of the metabolic properties of triglyceride-rich lipoproteins from human and mouse apoC-III transgenic mice. Journal of lipid research 85 8864964
1999 ApoCIII gene variants modulate postprandial response to both glucose and fat tolerance tests. Circulation 82 10199885
2019 Effects of APOC3 Heterozygous Deficiency on Plasma Lipid and Lipoprotein Metabolism. Arteriosclerosis, thrombosis, and vascular biology 78 30580564
2019 Emerging Evidence that ApoC-III Inhibitors Provide Novel Options to Reduce the Residual CVD. Current atherosclerosis reports 74 31111320
1997 Common genomic variation in the APOC3 promoter associated with variation in plasma lipoproteins. Arteriosclerosis, thrombosis, and vascular biology 70 9409252
1988 DNA polymorphism haplotypes of the human apolipoprotein APOA1-APOC3-APOA4 gene cluster. Human genetics 70 2903847
1985 Isolation and characterization of cDNA clones corresponding to two different human apoC-III alleles. Journal of lipid research 70 2989400
2006 Associations among race/ethnicity, ApoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy. PLoS medicine 67 16417409
2011 The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3 I148M genotype in patients with nonalcoholic fatty liver. Journal of hepatology 66 21777557
2022 Broadening the Scope of Dyslipidemia Therapy by Targeting APOC3 (Apolipoprotein C3) and ANGPTL3 (Angiopoietin-Like Protein 3). Arteriosclerosis, thrombosis, and vascular biology 65 36579649
2010 Regulation of hepatic ApoC3 expression by PGC-1β mediates hypolipidemic effect of nicotinic acid. Cell metabolism 65 20889132
1989 A regulatory element in the ApoCIII promoter that directs hepatic specific transcription binds to proteins in expressing and nonexpressing cell types. The Journal of biological chemistry 60 2777781
2002 ApoC-III gene polymorphisms and risk of coronary artery disease. Journal of lipid research 58 12235176
2013 A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population. Obesity (Silver Spring, Md.) 57 23512881
2015 Aggravated restenosis and atherogenesis in ApoCIII transgenic mice but lack of protection in ApoCIII knockouts: the effect of authentic triglyceride-rich lipoproteins with and without ApoCIII. Cardiovascular research 56 26160324
2017 The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis. Atherosclerosis 55 28865324
2010 Functional analysis of the missense APOC3 mutation Ala23Thr associated with human hypotriglyceridemia. Journal of lipid research 54 20097930
2009 Synthesis of reconstituted high density lipoprotein (rHDL) containing apoA-I and apoC-III: the functional role of apoC-III in rHDL. Molecules and cells 54 19326075
1990 Intracellular modification of human apolipoprotein AII (apoAII) and sites of apoAII mRNA synthesis: comparison of apoAII with apoCII and apoCIII isoproteins. Biochemistry 51 2108716
2005 APOC3/A5 haplotypes, lipid levels, and risk of myocardial infarction in the Central Valley of Costa Rica. Journal of lipid research 49 16192625
1995 Complex interactions between SP1 bound to multiple distal regulatory sites and HNF-4 bound to the proximal promoter lead to transcriptional activation of liver-specific human APOCIII gene. Biochemistry 49 7640286
2019 ApoC-III ASO promotes tissue LPL activity in the absence of apoE-mediated TRL clearance. Journal of lipid research 48 31092690
2006 Evidence for a complex relationship between apoA-V and apoC-III in patients with severe hypertriglyceridemia. Journal of lipid research 48 16861622
1999 Binding specificity and modulation of the human ApoCIII promoter activity by heterodimers of ligand-dependent nuclear receptors. Biochemistry 48 9893992
2007 Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice. Journal of lipid research 47 17438339
2013 Abdominal fat interacts with PNPLA3 I148M, but not with the APOC3 variant in the pathogenesis of liver steatosis in chronic hepatitis C. Journal of viral hepatitis 46 23808989
2015 Decreased expression of the APOA1-APOC3-APOA4 gene cluster is associated with risk of Alzheimer's disease. Drug design, development and therapy 45 26491253
2012 Genetic variation in PNPLA3 but not APOC3 influences liver fat in non-alcoholic fatty liver disease. Journal of gastroenterology and hepatology 44 22141340
2021 Pharmacological Inhibition of CETP (Cholesteryl Ester Transfer Protein) Increases HDL (High-Density Lipoprotein) That Contains ApoC3 and Other HDL Subspecies Associated With Higher Risk of Coronary Heart Disease. Arteriosclerosis, thrombosis, and vascular biology 43 34937388
2003 The study of APOA1, APOC3 and APOA4 variability in healthy ageing people reveals another paradox in the oldest old subjects. Annals of human genetics 42 12556235
1999 Mitogen-activated protein kinase regulates transcription of the ApoCIII gene. Involvement of the orphan nuclear receptor HNF4. The Journal of biological chemistry 42 10551874
2021 ApoC-III is a novel inducer of calcification in human aortic valves. The Journal of biological chemistry 41 33334888
2020 ApoCIII: A multifaceted protein in cardiometabolic disease. Metabolism: clinical and experimental 41 33058850
2017 ApoCIII as a Cardiovascular Risk Factor and Modulation by the Novel Lipid-Lowering Agent Volanesorsen. Current atherosclerosis reports 41 29124482
2000 SMAD proteins transactivate the human ApoCIII promoter by interacting physically and functionally with hepatocyte nuclear factor 4. The Journal of biological chemistry 38 10995777
1987 Molecular cloning of a human apoC-III variant: Thr 74----Ala 74 mutation prevents O-glycosylation. Journal of lipid research 38 3123586
1979 Lateral mobility of an amphipathic apolipoprotein, ApoC-III, bound to phosphatidylcholine bilayers with and without cholesterol. Proceedings of the National Academy of Sciences of the United States of America 37 293667
2008 ApoE epsilon2/epsilon3/epsilon4 polymorphism, ApoC-III/ApoE ratio and metabolic syndrome. Clinical and experimental medicine 36 18188530
2007 Association between the -455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample. BMC medical genetics 36 18096054
1994 Apo CIII gene transcription is regulated by a cytokine inducible NF-kappa B element. Nucleic acids research 36 8036173
1988 Mutagenesis of the glycosylation site of human ApoCIII. O-linked glycosylation is not required for ApoCIII secretion and lipid binding. The Journal of biological chemistry 36 3192519
1999 Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia. Journal of lipid research 34 10357835
2017 Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine. Journal of lipid research 33 28159868
2006 The effect of APOA5 and APOC3 variants on lipid parameters in European Whites, Indian Asians and Afro-Caribbeans with type 2 diabetes. Biochimica et biophysica acta 33 17197160
2018 APOC-III Antisense Oligonucleotides: A New Option for the Treatment of Hypertriglyceridemia. Current medicinal chemistry 32 28595549
2003 Plasma turnover of HDL apoC-I, apoC-III, and apoE in humans: in vivo evidence for a link between HDL apoC-III and apoA-I metabolism. Journal of lipid research 32 12867543
2003 Interaction between the APOC3 gene promoter polymorphisms, saturated fat intake and plasma lipoproteins. Atherosclerosis 32 14612212
2000 Plasma levels of remnant particles are determined in part by variation in the APOC3 gene insulin response element and the APOCI-APOE cluster. Journal of lipid research 32 10884292
2024 Drug-target Mendelian randomization analysis supports lowering plasma ANGPTL3, ANGPTL4, and APOC3 levels as strategies for reducing cardiovascular disease risk. European heart journal open 31 38895109
2014 Rare variant APOC3 R19X is associated with cardio-protective profiles in a diverse population-based survey as part of the Epidemiologic Architecture for Genes Linked to Environment Study. Circulation. Cardiovascular genetics 31 25363704
2006 Longitudinal analysis of haplotypes and polymorphisms of the APOA5 and APOC3 genes associated with variation in serum triglyceride levels: the Bogalusa Heart Study. Metabolism: clinical and experimental 31 17142127
2023 Advances in Dyslipidaemia Treatments: Focusing on ApoC3 and ANGPTL3 Inhibitors. Journal of lipid and atherosclerosis 30 38299167
2019 ApoC-III Glycoforms Are Differentially Cleared by Hepatic TRL (Triglyceride-Rich Lipoprotein) Receptors. Arteriosclerosis, thrombosis, and vascular biology 30 31390883
2018 New medications targeting triglyceride-rich lipoproteins: Can inhibition of ANGPTL3 or apoC-III reduce the residual cardiovascular risk? Atherosclerosis 30 29544086
2016 Targeting ApoC-III to Reduce Coronary Disease Risk. Current atherosclerosis reports 30 27443326
2015 Associations of the APOC3 rs5128 polymorphism with plasma APOC3 and lipid levels: a meta-analysis. Lipids in health and disease 29 25928461
2000 A hormone response element in the human apolipoprotein CIII (ApoCIII) enhancer is essential for intestinal expression of the ApoA-I and ApoCIII genes and contributes to the hepatic expression of the two linked genes in transgenic mice. The Journal of biological chemistry 29 10893424
2024 APOC3 siRNA and ASO therapy for dyslipidemia. Current opinion in endocrinology, diabetes, and obesity 27 38334488
2021 APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups. Lipids in health and disease 26 34548093
2006 Susceptibility to type 1 diabetes is associated with ApoCIII gene haplotypes. Diabetes 26 16505251
2001 Interaction of the common apolipoprotein C-III (APOC3 -482C > T) and hepatic lipase (LIPC -514C > T) promoter variants affects glucose tolerance in young adults. European Atherosclerosis Research Study II (EARS-II). Annals of human genetics 26 11427182
2022 Postprandial metabolism of apolipoproteins B48, B100, C-III, and E in humans with APOC3 loss-of-function mutations. JCI insight 25 36040803
2021 Guanidinylated Apolipoprotein C3 (ApoC3) Associates with Kidney and Vascular Injury. Journal of the American Society of Nephrology : JASN 25 34588185
2004 Storage of human plasma samples leads to alterations in the lipoprotein distribution of apoC-III and apoE. Journal of lipid research 25 15145987
2007 Association between plasma lipid parameters and APOC3 genotypes in Brazilian subjects: effect of gender, smoking and APOE genotypes. Clinica chimica acta; international journal of clinical chemistry 24 17367769
2003 Evidence of linkage of HDL level variation to APOC3 in two samples with different ascertainment. Human genetics 24 14569462
2025 Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia. The New England journal of medicine 23 40888739
2019 Intestinal basolateral lipid substrate transport is linked to chylomicron secretion and is regulated by apoC-III. Journal of lipid research 23 31152000
2016 Metabolic Characterization of a Rare Genetic Variation Within APOC3 and Its Lipoprotein Lipase-Independent Effects. Circulation. Cardiovascular genetics 23 27114411
2016 APOC3 induces endothelial dysfunction through TNF-α and JAM-1. Lipids in health and disease 23 27619170
2016 An APOC3 3'UTR variant associated with plasma triglycerides levels and coronary heart disease by creating a functional miR-4271 binding site. Scientific reports 23 27624799
2005 ApoC-III deficiency prevents hyperlipidemia induced by apoE overexpression. Journal of lipid research 23 15863838
1998 Transactivation of the ApoCIII promoter by ATF-2 and repression by members of the Jun family. Biochemistry 23 9760243
2017 Identity-by-Descent Mapping Identifies Major Locus for Serum Triglycerides in Amerindians Largely Explained by an APOC3 Founder Mutation. Circulation. Cardiovascular genetics 22 29237685
2006 Use of Intralipid for kinetic analysis of HDL apoC-III: evidence for a homogeneous kinetic pool of apoC-III in plasma. Journal of lipid research 22 16556931
2020 MicroRNA-424-5p regulates aortic smooth muscle cell function in atherosclerosis by blocking APOC3-mediated nuclear factor-κB signalling pathway. Experimental physiology 21 31912930
2016 Very low-depth sequencing in a founder population identifies a cardioprotective APOC3 signal missed by genome-wide imputation. Human molecular genetics 20 27146844
2000 The SP1 sites of the human apoCIII enhancer are essential for the expression of the apoCIII gene and contribute to the hepatic and intestinal expression of the apoA-I gene in transgenic mice. Nucleic acids research 20 11121483