ArticleThe Journal of biological chemistry2015
K Domain CR9 of Low Density Lipoprotein (LDL) Receptor-related Protein 1 (LRP1) Is Critical for Aggregated LDL-induced Foam Cell Formation from Human Vascular Smooth Muscle Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Unraveling the Role of LRP1 in Alzheimer's Disease: A Focus on Aβ Clearance and the Liver-Brain Axis.Journal of molecular neuroscience : MN · 2025Pooled it
- Foam Cells: The Origin of Formation and Target for Plant-derived Bioactive Compounds.Current medicinal chemistry · 2026Review
- Reduced Growth and Inflammation in Lrp5Journal of cellular and molecular medicine · 2025Article
- Vascular Smooth Muscle Cells: A Therapeutic Target in Atherosclerosis.Reviews in cardiovascular medicine · 2025Review
- Reduced blood EPAC1 protein levels as a marker of severe coronary artery disease: the role of hypoxic foam cell-transformed smooth muscle cells.Journal of translational medicine · 2025Article
- LRP1 immunotherapy enhances cardiomyocyte respiration by restricting cholesteryl ester accumulation in mitochondria.Journal of lipid research · 2025Article
- Stress, Vascular Smooth Muscle Cell Phenotype and Atherosclerosis: Novel Insight into Smooth Muscle Cell Phenotypic Transition in Atherosclerosis.Current atherosclerosis reports · 2024Review
- Therapeutic peptides for coronary artery diseases: in silico methods and current perspectives.Amino acids · 2024Review
- Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis: Current Knowledge and Future Perspectives.Current medical science · 2024Review
- An update on ox-LDL-inducing vascular smooth muscle cell-derived foam cells in atherosclerosis.Frontiers in cell and developmental biology · 2024Review
- Mechanisms modulating foam cell formation in the arterial intima: exploring new therapeutic opportunities in atherosclerosis.Frontiers in cardiovascular medicine · 2024Review
- Inhibitory Effects of LRP1-Based Immunotherapy on Cardiac Extracellular Matrix Biophysical Alterations Induced by Hypercholesterolemia.Journal of medicinal chemistry · 2023Article
- Soluble low-density lipoprotein receptor-related protein 1 as a surrogate marker of carotid plaque inflammation assessed byJournal of translational medicine · 2023Article
- Genetic heterogeneity in cardiovascular disease across ancestries: Insights for mechanisms and therapeutic intervention.Cambridge prisms. Precision medicine · 2023Review
- PCSK-9 inhibitors: a new direction for the future treatment of ischemic stroke.Frontiers in pharmacology · 2023Review
- Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation.Nature cardiovascular research · 2022Article
- Macrophage-, Dendritic-, Smooth Muscle-, Endothelium-, and Stem Cells-Derived Foam Cells in Atherosclerosis.International journal of molecular sciences · 2022Review
- Article
- Decreased low-density lipoprotein receptor-related protein 1 expression in pro-inflammatory monocytes is associated with subclinical atherosclerosis.Frontiers in cardiovascular medicine · 2022Article
- Lipid accumulation and novel insight into vascular smooth muscle cells in atherosclerosis.Journal of molecular medicine (Berlin, Germany) · 2021Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low density lipoprotein receptor-related protein (LRP1) mediates the internalization of aggregated LDL (AgLDL), which in turn increases the expression of LRP1 in human vascular smooth muscle cells (hVSMCs). This positive feedback mechanism is thus highly efficient to promote the formation of hVSMC foam cells, a crucial vascular component determining the susceptibility of atherosclerotic plaque to rupture. Here we have determined the LRP1 domains involved in AgLDL recognition with the aim of specifically blocking AgLDL internalization in hVSMCs. The capacity of fluorescently labeled AgLDL to bind to functional LRP1 clusters was tested in a receptor-ligand fluorometric assay made by immobilizing soluble LRP1 "minireceptors" (sLRP1-II, sLRP1-III, and sLRP1-IV) recombinantly expressed in CHO cells. This assay showed that AgLDL binds to cluster II. We predicted three well exposed and potentially immunogenic peptides in the CR7-CR9 domains of this cluster (termed P1 (Cys(1051)-Glu(1066)), P2 (Asp(1090)-Cys(1104)), and P3 (Gly(1127)-Cys(1140))). AgLDL, but not native LDL, bound specifically and tightly to P3-coated wells. Rabbit polyclonal antibodies raised against P3 prevented AgLDL uptake by hVSMCs and were almost twice as effective as anti-P1 and anti-P2 Abs in reducing intracellular cholesteryl ester accumulation. Moreover, anti-P3 Abs efficiently prevented AgLDL-induced LRP1 up-regulation and counteracted the down-regulatory effect of AgLDL on hVSMC migration. In conclusion, domain CR9 appears to be critical for LRP1-mediated AgLDL binding and internalization in hVSMCs. Our results open new avenues for an innovative anti-VSMC foam cell-based strategy for the treatment of vascular lipid deposition in atherosclerosis.
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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.