ArticleProceedings of the National Academy of Sciences of the United States of America2014
Genetic variants of ApoE and ApoER2 differentially modulate endothelial function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 73 citations in OpenAlex.
- Longitudinal effects of cerebrovascular reactivity and cerebral pulsatility in cognitively intact older adults with APOE4: links with cognition.GeroScience · 2026Article
- Role Shift of Glial Cells from Physiology to Pathology in Alzheimer's Disease: The Regulatory Impact of Exercise.Neuroscience bulletin · 2026Review
- Aortic Single-Cell Transcriptome Analysis Reveals ApoE-Isoform-Specific Influences on Vascular Disease.International journal of molecular sciences · 2026Article
- Article
- APOE Lipoprotein Particles: Pathophysiology, Therapy, and the Crosstalk in Alzheimer's Disease and Cardiovascular Disease.Molecular neurobiology · 2025Review
- Review
- 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
- ApoE4 requires lipidation enhancement to resolve cellular lipid and protein abnormalities following NPC1 inhibition.Scientific reports · 2025Article
- ApoE Receptor-2 R952Q Variant in Macrophages Elevates Soluble LRP1 to Potentiate Hyperlipidemia and Accelerate Atherosclerosis in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Constitutive NOS Production Is Modulated by Alzheimer's Disease Pathology Depending on APOE Genotype.International journal of molecular sciences · 2024Article
- Roles of peripheral lipoproteins and cholesteryl ester transfer protein in the vascular contributions to cognitive impairment and dementia.Molecular neurodegeneration · 2023Review
- Macrophage-to-endothelial cell crosstalk by the cholesterol metabolite 27HC promotes atherosclerosis in male mice.Nature communications · 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
- Review
- Apolipoprotein E in Cardiometabolic and Neurological Health and Diseases.International journal of molecular sciences · 2022Review
- 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
- Characterization of the blood-brain barrier in genetically diverse laboratory mouse strains.Fluids and barriers of the CNS · 2021Article
- Lipoprotein receptor signalling in atherosclerosis.Cardiovascular research · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
It is poorly understood why there is greater cardiovascular disease risk associated with the apolipoprotein E4 (apoE) allele vs. apoE3, and also greater risk with the LRP8/apolipoprotein E receptor 2 (ApoER2) variant ApoER2-R952Q. Little is known about the function of the apoE-ApoER2 tandem outside of the central nervous system. We now report that in endothelial cells apoE3 binding to ApoER2 stimulates endothelial NO synthase (eNOS) and endothelial cell migration, and it also attenuates monocyte-endothelial cell adhesion. However, apoE4 does not stimulate eNOS or endothelial cell migration or dampen cell adhesion, and alternatively it selectively antagonizes apoE3/ApoER2 actions. The contrasting endothelial actions of apoE4 vs. apoE3 require the N-terminal to C-terminal interaction in apoE4 that distinguishes it structurally from apoE3. Reconstitution experiments further reveal that ApoER2-R952Q is a loss-of-function variant of the receptor in endothelium. Carotid artery reendothelialization is decreased in ApoER2(-/-) mice, and whereas adenoviral-driven apoE3 expression in wild-type mice has no effect, apoE4 impairs reendothelialization. Moreover, in a model of neointima formation invoked by carotid artery endothelial denudation, ApoER2(-/-) mice display exaggerated neointima development. Thus, the apoE3/ApoER2 tandem promotes endothelial NO production, endothelial repair, and endothelial anti-inflammatory properties, and it prevents neointima formation. In contrast, apoE4 and ApoER2-R952Q display dominant-negative action and loss of function, respectively. Thus, genetic variants of apoE and ApoER2 impact cardiovascular health by differentially modulating endothelial function.
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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.