ArticleAtherosclerosis2016
The P2Y2 receptor mediates uptake of matrix-retained and aggregated low density lipoprotein in primary vascular smooth muscle cells.
Article in Atherosclerosis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Foam cells: tracing the diverse cellular origins and their linked signaling pathways.Journal of translational medicine · 2025Review
- Vascular Smooth Muscle Cells: A Therapeutic Target in Atherosclerosis.Reviews in cardiovascular medicine · 2025Review
- The potential of ARL4C and its-mediated genes in atherosclerosis and agent development.Frontiers in pharmacology · 2025Review
- Long non-coding RNA SNHG12 regulates leptomeningeal collateral remodeling via RGMa after ischemic stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Stress, Vascular Smooth Muscle Cell Phenotype and Atherosclerosis: Novel Insight into Smooth Muscle Cell Phenotypic Transition in Atherosclerosis.Current atherosclerosis reports · 2024Review
- Design, Synthesis, and Evaluation of a New Chemotype Fluorescent Ligand for the P2YACS medicinal chemistry letters · 2024Article
- Mechanisms modulating foam cell formation in the arterial intima: exploring new therapeutic opportunities in atherosclerosis.Frontiers in cardiovascular medicine · 2024Review
- RGMa promotes dedifferentiation of vascular smooth muscle cells into a macrophage-like phenotype in vivo and in vitro.Journal of lipid research · 2022Article
- Smooth Muscle Cell-Macrophage Interactions Leading to Foam Cell Formation in Atherosclerosis: Location, Location, Location.Frontiers in physiology · 2022Review
- Lipid accumulation and novel insight into vascular smooth muscle cells in atherosclerosis.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Filamin A Regulates Cardiovascular Remodeling.International journal of molecular sciences · 2021Review
- Article
- Association of G-protein coupled purinergic receptor P2Y2 with ischemic stroke in a Han Chinese population of North China.Neural regeneration research · 2019Article
- The Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Lipid Metabolism, Glucose Homeostasis and Inflammation.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsThe internalization of aggregated low-density lipoproteins (agLDL) mediated by low-density lipoprotein receptor related protein (LRP1) may involve the actin cytoskeleton in ways that differ from the endocytosis of soluble LDL by the LDL receptor (LDLR). This study aims to define novel mechanisms of agLDL uptake through modulation of the actin cytoskeleton, to identify molecular targets involved in foam cell formation in vascular smooth muscle cells (VSMCs). The critical observation that formed the basis for these studies is that under pathophysiological conditions, nucleotide release from blood-derived and vascular cells activates SMC P2Y2 receptors (P2Y2Rs) leading to rearrangement of the actin cytoskeleton and cell motility. Therefore, we tested the hypothesis that P2Y2R activation mediates agLDL uptake by VSMCs.
methodsPrimary VSMCs were isolated from aortas of wild type (WT) C57BL/6 and.P2Y2R-/- mice to investigate whether P2Y2R activation modulates LRP1 expression. Cells were transiently transfected with cDNA encoding a hemagglutinin-tagged (HA-tagged) WT P2Y2R, or a mutant P2Y2R that unlike the WT P2Y2R does not bind the cytoskeletal actin-binding protein filamin-A (FLN-A).
resultsP2Y2R activation significantly increased agLDL uptake, and LRP1 mRNA expression decreased in P2Y2R-/- VSMCs versus WT. SMCs, expressing P2Y2R defective in FLN-A binding, exhibit 3-fold lower LDLR expression levels than SMCs expressing WT P2Y2R, while cells transfected with WT P2Y2R show greater agLDL uptake in both WT and P2Y2R-/- VSMCs versus cells transfected with the mutant P2Y2R.
conclusionsTogether, these results show that both LRP1 and LDLR expression and agLDL uptake are regulated by P2Y2R in VSMCs, and that agLDL uptake due to P2Y2R activation is dependent upon cytoskeletal reorganization mediated by P2Y2R binding to FLN-A.
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