ArticleNature medicine2017
A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- Review
- Olezarsen for the Treatment of Hypertriglyceridemia.Methods in molecular biology (Clifton, N.J.) · 2026Review
- A novel lncRNA GM47544 modulates triglyceride metabolism by inducing ubiquitination-dependent protein degradation of APOC3.Molecular metabolism · 2024Article
- Review
- Article
- Hyperlipidaemia in diabetes: are there particular considerations for next-generation therapies?Diabetologia · 2024Review
- Exploring apolipoprotein C-III: pathophysiological and pharmacological relevance.Cardiovascular research · 2024Review
- Higher remnant cholesterol increases the risk of coronary heart disease and diabetes in postmenopausal women.Frontiers in endocrinology · 2024Article
- Advances in Dyslipidaemia Treatments: Focusing on ApoC3 and ANGPTL3 Inhibitors.Journal of lipid and atherosclerosis · 2024Review
- Apolipoprotein C3: form begets function.Journal of lipid research · 2024Review
- Apolipoprotein C-III itself stimulates the Syk/cPLA2-induced inflammasome activation of macrophage to boost anti-tumor activity of CD8Cancer immunology, immunotherapy : CII · 2023Article
- Advances in Treatment of Dyslipidemia.International journal of molecular sciences · 2023Review
- APOC-III: a Gatekeeper in Controlling Triglyceride Metabolism.Current atherosclerosis reports · 2023Review
- New Therapeutic Approaches to the Treatment of Dyslipidemia 1: ApoC-III and ANGPTL3.Journal of lipid and atherosclerosis · 2023Review
- Gain-of-Function Variants in Lipid Genes Enhance Biological Insight and Point Toward Therapeutic Opportunities.Circulation · 2022Article
- Endothelial Lipid Metabolism.Cold Spring Harbor perspectives in medicine · 2022Review
- Is apoCIII-Lowering A Double-Edged Sword?Journal of atherosclerosis and thrombosis · 2022Article
- Childhood Hypertriglyceridemia: Is It Time for a New Approach?Current atherosclerosis reports · 2022Review
- A Tale of Two New Targets for Hypertriglyceridaemia: Which Choice of Therapy?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
Abstract
Recent large-scale genetic sequencing efforts have identified rare coding variants in genes in the triglyceride-rich lipoprotein (TRL) clearance pathway that are protective against coronary heart disease (CHD), independently of LDL cholesterol (LDL-C) levels. Insight into the mechanisms of protection of these variants may facilitate the development of new therapies for lowering TRL levels. The gene APOC3 encodes apoC-III, a critical inhibitor of triglyceride (TG) lipolysis and remnant TRL clearance. Here we report a detailed interrogation of the mechanism of TRL lowering by the APOC3 Ala43Thr (A43T) variant, the only missense (rather than protein-truncating) variant in APOC3 reported to be TG lowering and protective against CHD. We found that both human APOC3 A43T heterozygotes and mice expressing human APOC3 A43T display markedly reduced circulating apoC-III levels. In mice, this reduction is due to impaired binding of A43T apoC-III to lipoproteins and accelerated renal catabolism of free apoC-III. Moreover, the reduced content of apoC-III in TRLs resulted in accelerated clearance of circulating TRLs. On the basis of this protective mechanism, we developed a monoclonal antibody targeting lipoprotein-bound human apoC-III that promotes circulating apoC-III clearance in mice expressing human APOC3 and enhances TRL catabolism in vivo. These data reveal the molecular mechanism by which a missense variant in APOC3 causes reduced circulating TG levels and, hence, protects from CHD. This protective mechanism has the potential to be exploited as a new therapeutic approach to reduce apoC-III levels and circulating TRL burden.
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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 Socratic graph.