Trial reportJCI insight2018
Apolipoproteins E and CIII interact to regulate HDL metabolism and coronary heart disease risk.
Trial report in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01399632 (Dietary Fat and High-Density Lipoprotein), which is not on this map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Dietary Fat and High-Density Lipoprotein (HDL) Metabolism-Effect of Carbohydrate and Fat Intake
Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease.Nature genetics · 2023Pooled it
- Partially Replacing Dietary Carbohydrate With Unsaturated Fat or Protein Shifts Protein-Based HDL Subspecies Toward Lower Coronary Heart Disease Risk.Arteriosclerosis, thrombosis, and vascular biology · 2026Trial
- 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 · 2022Trial
- Associations of Perfluoroalkyl substances with blood lipids and Apolipoproteins in lipoprotein subspecies: the POUNDS-lost study.Environmental health : a global access science source · 2020Trial
- Effects of Replacing Dietary Monounsaturated Fat With Carbohydrate on HDL (High-Density Lipoprotein) Protein Metabolism and Proteome Composition in Humans.Arteriosclerosis, thrombosis, and vascular biology · 2019Trial
- Cholesterol efflux capacity, HDL cholesterol, and risk of coronary heart disease: a nested case-control study in men.Journal of lipid research · 2019Trial
- Dietary unsaturated fat increases HDL metabolic pathways involving apoE favorable to reverse cholesterol transport.JCI insight · 2019Trial
- Apolipoprotein E Mimetic Peptide-Mediated Modulation of Lipid Homeostasis.Biomolecules · 2026Review
- Exploring the role of inflammatory cytokines in obesity-mediated MASLD development and drug target identification.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Review
- Current Understanding of Circulating Apolipoprotein E-Containing High-Density Lipoproteins and Their Clinical Utility in Cardiovascular Disease Risk Assessment.Yonago acta medica · 2026Review
- ABCA1-Mediated Structural Diversity of HDL Subspecies and Their Proposed Roles in Cardioprotection.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Atherogenic apolipoprotein C-III may not be as bad as we thought.Journal of thrombosis and haemostasis : JTH · 2026Article
- The Structural and Functional Journey of Apolipoprotein A-I Through the Human Body.Current atherosclerosis reports · 2026Review
- Apolipoprotein E-Containing High-Density Lipoprotein is Independently Associated with Atherosclerotic Plaque Progression.Journal of atherosclerosis and thrombosis · 2026Article
- Inventive HDL Mimicking Nanoparticles: A Promising Frontier in Cardiovascular Disease Management.Cardiovascular toxicology · 2025Review
- Effect of Guava Seeds on the Biochemical Parameters and Composition of HDL Subclasses in Ovariectomized Rats.Antioxidants (Basel, Switzerland) · 2025Article
- Investigating the molecular mechanisms and clinical potential of APO+ endothelial cells associated with PANoptosis in the tumor microenvironment of hepatocellular carcinoma using single-cell sequencing data.Translational oncology · 2025Article
- Relevance of Lipoprotein Composition in Endothelial Dysfunction and the Development of Hypertension.International journal of molecular sciences · 2025Review
- Reduced Oxidative Susceptibility of Lp(a) and LDL Fractions as a Pleiotropic Effect of Lipoprotein Apheresis in Patients with Elevated Lp(a) and ASCVDs.International journal of molecular sciences · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundSubspecies of HDL contain apolipoprotein E (apoE) and/or apoCIII. Both proteins have properties that could affect HDL metabolism. The relation between HDL metabolism and risk of coronary heart disease (CHD) is not well understood.
methodsEighteen participants were given a bolus infusion of [D3]L-leucine to label endogenous proteins on HDL. HDL was separated into subspecies containing apoE and/or apoCIII and then into 4 sizes. Metabolic rates for apoA-I in HDL subspecies and sizes were determined by interactive modeling. The concentrations of apoE in HDL that contain or lack apoCIII were measured in a prospective study in Denmark including 1,949 incident CHD cases during 9 years.
resultsHDL containing apoE but not apoCIII is disproportionately secreted into the circulation, actively expands while circulating, and is quickly cleared. These are key metabolic steps in reverse cholesterol transport, which may protect against atherosclerosis. ApoCIII on HDL strongly attenuates these metabolic actions of HDL apoE. In the epidemiological study, the relation between HDL apoE concentration and CHD significantly differed depending on whether apoCIII was present. HDL apoE was associated significantly with lower risk of CHD only in the HDL subspecies lacking apoCIII.
conclusionsApoE and apoCIII on HDL interact to affect metabolism and CHD. ApoE promotes metabolic steps in reverse cholesterol transport and is associated with lower risk of CHD. ApoCIII, when coexisting with apoE on HDL, abolishes these benefits. Therefore, differences in metabolism of HDL subspecies pertaining to reverse cholesterol transport are reflected in differences in association with CHD.
trial registrationClinicaltrials.gov NCT01399632.
fundingThis work was supported by NIH grant R01HL095964 to FMS and by a grant to the Harvard Clinical and Translational Science Center (8UL1TR0001750) from the National Center for Advancing Translational Science.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.