ArticleBiochimica et biophysica acta2014
Apolipoprotein E receptor-2 deficiency enhances macrophage susceptibility to lipid accumulation and cell death to augment atherosclerotic plaque progression and necrosis.
Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Apolipoprotein E Gene Variants and Risk of Coronary Heart Disease: A Meta-Analysis.BioMed research international · 2016Pooled it
- Macrophagic Sclerostin Loop2-ApoER2 Interaction Required by Sclerostin for Cardiovascular Protective Action.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LRP8 Regulates Lipid Metabolism to Stimulate Malignant Progression and Cisplatin Resistance in Bladder Cancer.The Kaohsiung journal of medical sciences · 2025Article
- Distinct Roles of apoE Receptor-2 Cytoplasmic Domain Splice Variants in Cardiometabolic Disease Modulation.Biomedicines · 2025Article
- Role of Sclerostin in Cardiovascular System.International journal of molecular sciences · 2025Review
- Genetic or therapeutic disruption of the Reelin/Apoer2 signaling pathway improves inflammatory arthritis outcomes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Leukocyte-lymphatic intersections during cardiac inflammation.Journal of molecular and cellular cardiology · 2025Review
- ApoE Receptor-2 R952Q Variant in Macrophages Elevates Soluble LRP1 to Potentiate Hyperlipidemia and Accelerate Atherosclerosis in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Lipid-Lowering Drugs and Pulmonary Vascular Disease: A Mendelian Randomization Study.Pulmonary circulation · 2025Article
- Assessing the impact of evolocumab on thin-cap fibroatheroma and endothelial function in patients with very high-risk atherosclerotic cardiovascular disease: a study protocol for a randomized controlled trial.Cardiovascular diagnosis and therapy · 2024Article
- Evidence that Alzheimer's Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry.Journal of Alzheimer's disease : JAD · 2024Review
- Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice.Cardiovascular diabetology · 2023Article
- Different sensitivity to diet-induced hyperinsulinemia and hyperglycemia between mice with global or bone marrow-specific apoE receptor-2 deficiency.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Low-Density Lipoprotein Receptor-Related Protein 8 at the Crossroad between Cancer and Neurodegeneration.International journal of molecular sciences · 2022Review
- Interplay of Low-Density Lipoprotein Receptors, LRPs, and Lipoproteins in Pulmonary Hypertension.JACC. Basic to translational science · 2022Review
- PCSK9 Biology and Its Role in Atherothrombosis.International journal of molecular sciences · 2021Review
- Reelin Depletion Protects Against Atherosclerosis by Decreasing Vascular Adhesion of Leukocytes.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- PCSK9 Functions in Atherosclerosis Are Not Limited to Plasmatic LDL-Cholesterol Regulation.Frontiers in cardiovascular medicine · 2021Review
- An Update on the Role of PCSK9 in Atherosclerosis.Journal of atherosclerosis and thrombosis · 2020Review
- Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Genome-wide association studies have linked LRP8 polymorphisms to premature coronary artery disease and myocardial infarction in humans. However, the mechanisms by which dysfunctions of apolipoprotein E receptor-2 (apoER2), the protein encoded by LRP8 gene, influence atherosclerosis have not been elucidated completely. The current study focused on the role of apoER2 in macrophages, a cell type that plays an important role in atherosclerosis. Results showed that apoER2-deficient mouse macrophages accumulated more lipids and were more susceptible to oxidized LDL (oxLDL)-induced death compared to control cells. Consistent with these findings, apoER2 deficient macrophages also displayed defective serum-induced Akt activation and higher levels of the pro-apoptotic protein phosphorylated p53. Furthermore, the expression and activation of peroxisome proliferator-activated receptor γ (PPARγ) were increased in apoER2-deficient macrophages. Deficiency of apoER2 in hypercholesterolemic LDL receptor-null mice (Lrp8(-/-)Ldlr(-/-) mice) also resulted in accelerated atherosclerosis with more complex lesions and extensive lesion necrosis compared to Lrp8(+/+)Ldlr(-/-) mice. The atherosclerotic plaques of Lrp8(-/-)Ldlr(-/-) mice displayed significantly higher levels of p53-positive macrophages, indicating that the apoER2-deficient macrophages contribute to the accelerated atherosclerotic lesion necrosis observed in these animals. Taken together, this study indicates that apoER2 in macrophages limits PPARγ expression and protects against oxLDL-induced cell death. Thus, abnormal apoER2 functions in macrophages may at least in part contribute to the premature coronary artery disease and myocardial infarction in humans with LRP8 polymorphisms. Moreover, the elevated PPARγ expression in apoER2-deficient macrophages suggests that LRP8 polymorphism may be a genetic modifier of cardiovascular risk with PPARγ therapy.
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Registered trials
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