ArticleEuropean heart journal2024
Genetic inhibition of angiopoietin-like protein-3, lipids, and cardiometabolic risk.
Article in European heart journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Integrative genetic and liver transcriptomic analyses identify TRIB1AL as a target for steatotic liver disease.The Journal of clinical endocrinology and metabolism · 2026Pooled it
- Evinacumab Across Different Lipid Phenotypes: A Systematic Review and Meta-Analysis.Advances in therapy · 2026Article
- Review
- Investigation of the relationship between carotid intima-media thickness and angiopoietin-like factor 3 levels in metabolic dysfunction-associated steatotic liver disease.Scientific reports · 2026Article
- Research progress on targeted regulatory proteins in the prevention and treatment of atherosclerosis.Frontiers in immunology · 2026Review
- Heart-liver co-management: epidemiology, mechanisms, and novel therapeutic approaches for metabolic dysfunction-associated steatotic liver disease and coronary artery disease.Frontiers in cardiovascular medicine · 2026Review
- Prioritization of potential drug targets for diabetic kidney disease using integrative omics data mining and causal inference.Journal of pharmaceutical analysis · 2025Article
- RNA interference versus antibody-based PCSK9 inhibition for the prevention of cardiovascular disease: a drug-target Mendelian randomization study.Cardiovascular research · 2025Article
- CRISPR-Cas9 Targeting PCSK9: A Promising Therapeutic Approach for Atherosclerosis.Journal of cardiovascular translational research · 2025Review
- Associations between circulating amino acids and metabolic dysfunction-associated steatotic liver disease in individuals living with severe obesity.Physiological reports · 2025Article
- ANGPTL3 and residual atherosclerotic risk: from lipid metabolism to therapeutic targeting.Frontiers in endocrinology · 2025Review
- Review
- Drug-target Mendelian randomisation applied to metabolic dysfunction-associated steatotic liver disease: opportunities and challenges.eGastroenterology · 2024Review
- Genetic assessment of efficacy and safety profiles of coagulation cascade proteins identifies Factors II and XI as actionable anticoagulant targets.European heart journal open · 2024Article
- Drug-target Mendelian randomization analysis supports lowering plasma ANGPTL3, ANGPTL4, and APOC3 levels as strategies for reducing cardiovascular disease risk.European heart journal open · 2024Article
- Inhibiting angiopoietin-like protein 3: clear skies or clouds on the horizon?European heart journal · 2024Article
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17 authors at 2 institutions in 1 country.
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Abstract
BACKGROUND AND
aimsRNA-based, antibody-based, and genome editing-based therapies are currently under investigation to determine if the inhibition of angiopoietin-like protein-3 (ANGPTL3) could reduce lipoprotein-lipid levels and atherosclerotic cardiovascular disease (ASCVD) risk. Mendelian randomisation (MR) was used to determine whether genetic variations influencing ANGPTL3 liver gene expression, blood levels, and protein structure could causally influence triglyceride and apolipoprotein B (apoB) levels as well as coronary artery disease (CAD), ischaemic stroke (IS), and other cardiometabolic diseases.
methodsRNA sequencing of 246 explanted liver samples and genome-wide genotyping was performed to identify single-nucleotide polymorphisms (SNPs) associated with liver expression of ANGPTL3. Genome-wide summary statistics of plasma protein levels of ANGPTL3 from the deCODE study (n = 35 359) were used. A total of 647 carriers of ANGPTL3 protein-truncating variants (PTVs) associated with lower plasma triglyceride levels were identified in the UK Biobank. Two-sample MR using SNPs that influence ANGPTL3 liver expression or ANGPTL3 plasma protein levels as exposure and cardiometabolic diseases as outcomes was performed (CAD, IS, heart failure, non-alcoholic fatty liver disease, acute pancreatitis, and type 2 diabetes). The impact of rare PTVs influencing plasma triglyceride levels on apoB levels and CAD was also investigated in the UK Biobank.
resultsIn two-sample MR studies, common genetic variants influencing ANGPTL3 hepatic or blood expression levels of ANGPTL3 had a very strong effect on plasma triglyceride levels, a more modest effect on low-density lipoprotein cholesterol, a weaker effect on apoB levels, and no effect on CAD or other cardiometabolic diseases. In the UK Biobank, the carriers of rare ANGPTL3 PTVs providing lifelong reductions in median plasma triglyceride levels [-0.37 (interquartile range 0.41) mmol/L] had slightly lower apoB levels (-0.06 ± 0.32 g/L) and similar CAD event rates compared with non-carriers (10.2% vs. 10.9% in carriers vs. non-carriers, P = .60).
conclusionsPTVs influencing ANGPTL3 protein structure as well as common genetic variants influencing ANGPTL3 hepatic expression and/or blood protein levels exhibit a strong effect on circulating plasma triglyceride levels, a weak effect on circulating apoB levels, and no effect on ASCVD. Near-complete inhibition of ANGPTL3 function in patients with very elevated apoB levels may be required to reduce ASCVD risk.
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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.