ArticlePLoS genetics2021
Deficiency of ASGR1 in pigs recapitulates reduced risk factor for cardiovascular disease in humans.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Plasma proteome of the EAT-Lancet diet and long-term risks of cardiovascular disease and mortality.Food & function · 2026Article
- Proteome-wide genetic analyses identify ASGR1 as a potential biomarker linking smoking with ischemic heart disease.Nature cardiovascular research · 2026Article
- DNA methylation informs adult cardiovascular risk and prevention for low birthweight individuals.Journal of global health · 2026Article
- In vivo base editing of Asgr1 reduces blood lipids in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- ASGR1 Deficiency Promotes Liver Fibrosis by Enhancing Pro-Inflammatory Arachidonic Acid Metabolism and ALP Secretion.Immunity, inflammation and disease · 2026Article
- The asialoglycoprotein receptor 1 (ASGR1): emerging new roles in health and disease.Biomarker research · 2026Review
- Fisetin-loaded nanoparticles as a novel approach for cholesterol regulation in hypercholesterolemia: targeting the ASGR1-mediated mTORC1/AMPK pathway.Journal of nanobiotechnology · 2026Article
- Review
- Cross-sectional, interventional, and causal investigation of insulin sensitivity using plasma proteomics in diverse populations.Metabolism: clinical and experimental · 2025Article
- Cardiac rehabilitation in porcine models: Advances in therapeutic strategies for ischemic heart disease.Zoological research · 2025Review
- Pathways and Molecular Mechanisms Governing LDL Receptor Regulation.Circulation research · 2025Review
- Serum Soluble Asialoglycoprotein Receptor 1: A Potential Predictor Marker Linked to Type 2 Diabetes Mellitus, Demonstrating Positive Correlation With High Sensitive C-Reactive Protein.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Asialoglycoprotein receptor 1: a multifaceted receptor in the liver and cardiovascular system.Frontiers in medicine · 2025Review
- ASGR1 Deficiency Inhibits Atherosclerosis in Western Diet-FedArteriosclerosis, thrombosis, and vascular biology · 2024Article
- ASGR1 deficiency improves atherosclerosis but alters liver metabolism in ApoECardiovascular diabetology · 2024Article
- Review
- Article
- Deficiency of ASGR1 Alleviates Diet-Induced Systemic Insulin Resistance via Improved Hepatic Insulin Sensitivity.Diabetes & metabolism journal · 2024Article
- siRNA-mediated reduction of a circulating protein in swine using lipid nanoparticles.Molecular therapy. Methods & clinical development · 2024Article
- Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress.Nature communications · 2024Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic variants in the asialoglycoprotein receptor 1 (ASGR1) are associated with a reduced risk of cardiovascular disease (CVD) in humans. However, the underlying molecular mechanism remains elusive. Given the cardiovascular similarities between pigs and humans, we generated ASGR1-deficient pigs using the CRISPR/Cas9 system. These pigs show age-dependent low levels of non-HDL-C under standard diet. When received an atherogenic diet for 6 months, ASGR1-deficient pigs show lower levels of non-HDL-C and less atherosclerotic lesions than that of controls. Furthermore, by analysis of hepatic transcriptome and in vivo cholesterol metabolism, we show that ASGR1 deficiency reduces hepatic de novo cholesterol synthesis by downregulating 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and increases cholesterol clearance by upregulating the hepatic low-density lipoprotein receptor (LDLR), which together contribute to the low levels of non-HDL-C. Despite the cardioprotective effect, we unexpectedly observed mild to moderate hepatic injury in ASGR1-deficient pigs, which has not been documented in humans with ASGR1 variants. Thus, targeting ASGR1 might be an effective strategy to reduce hypercholesterolemia and atherosclerosis, whereas further clinical evidence is required to assess its hepatic impact.
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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.