ArticleFrontiers in cardiovascular medicine2021
The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels.
Article in Frontiers in cardiovascular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 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
- The asialoglycoprotein receptor 1 (ASGR1): emerging new roles in health and disease.Biomarker research · 2026Review
- Inhibition of the ANGPTL3/8 Complex for the Prevention and Treatment of Atherosclerotic Cardiovascular Disease.Current atherosclerosis reports · 2024Review
- A unified model for regulating lipoprotein lipase activity.Trends in endocrinology and metabolism: TEM · 2024Review
- Circumventing Cardiovascular Calamities: The Dawn of ANGPTL3 Blockade in Severe Dyslipidemia Management.Cardiovascular & hematological disorders drug targets · 2024Review
- Targeting ANGPTL3 by GalNAc-conjugated siRNAMolecular therapy. Nucleic acids · 2023Article
- Adolescent obesity and ANGPTL8: correlations with high sensitivity C-reactive protein, leptin, and chemerin.Frontiers in endocrinology · 2023Article
- An anti-ANGPTL3/8 antibody decreases circulating triglycerides by binding to a LPL-inhibitory leucine zipper-like motif.Journal of lipid research · 2022Article
- ANGPTL3 Is Involved in the Post-prandial Response in Triglyceride-Rich Lipoproteins and HDL Components in Patients With Coronary Artery Disease.Frontiers in cardiovascular medicine · 2022Article
- An updated ANGPTL3-4-8 model as a mechanism of triglyceride partitioning between fat and oxidative tissues.Progress in lipid research · 2022Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Elevated triglyceride (TG) and reduced high-density lipoprotein-cholesterol (HDL-C) plasma levels are risk factors for atherosclerosis and cardiovascular disease. Therefore, a drug that simultaneously reduces TG and increases HDL-C plasma levels has the potential to prevent and treat these diseases. Angiopoietin-like 3 (ANGPTL3) regulates plasma TG and HDL-C levels by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL), respectively. ANGPTL3 inhibition of LPL requires complex formation with ANGPTL8, which is not required for its inhibition of EL. Therefore, the entire pool of plasma ANGPTL3 can be classified as ANGPTL8-associated ANGPTL3 and ANGPTL8-free ANGPTL3, where the former inhibits LPL and the latter inhibits EL. ANGPTL8 antibodies or inhibitors that block its interactions with ANGPTL3 can disrupt or preclude the ANGPTL3-8 complex formation, resulting in fewer ANGPTL3-8 complexes (reduced LPL inhibition), but more free ANGPTL3 (enhanced EL inhibition). Therefore, ANGPTL8 antagonism increases LPL activity while decreasing EL activity, thus leading to reduced plasma TG while simultaneously increasing HDL-C levels. In humans, carriers of ANGPTL8 truncating variants consistently have lower TG but higher HDL-C levels, supporting this hypothesis.
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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 OpenQuestion graph.