ArticleArteriosclerosis, thrombosis, and vascular biology2016
Enzymatically Modified Low-Density Lipoprotein Promotes Foam Cell Formation in Smooth Muscle Cells via Macropinocytosis and Enhances Receptor-Mediated Uptake of Oxidized Low-Density Lipoprotein.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 75 citations in OpenAlex.
- Olfactomedin 2 Promotes Atherosclerosis by Eliciting Smooth Muscle Foam Cell Formation.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- KAP1 SUMOylates and stabilizes SR-A to facilitate glycated LDL transcytosis and accelerate atherosclerosis.Cellular & molecular biology letters · 2026Article
- Vascular Smooth Muscle Cells: A Therapeutic Target in Atherosclerosis.Reviews in cardiovascular medicine · 2025Review
- Dual-mode-driven nanomotors targeting inflammatory macrophages for the MRI and synergistic treatment of atherosclerosis.Journal of nanobiotechnology · 2025Article
- Endothelial Dysfunction in Atherosclerosis: Experimental Models and Therapeutics.Biomaterials research · 2025Review
- Activation of receptor-independent fluid-phase pinocytosis promotes foamy monocyte formation in atherosclerotic mice.Redox biology · 2024Article
- Nanoparticle-based itaconate treatment recapitulates low-cholesterol/low-fat diet-induced atherosclerotic plaque resolution.Cell reports · 2024Article
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- Unveiling impaired vascular function and cellular heterogeneity in diabetic donor-derived vascular organoids.Stem cells (Dayton, Ohio) · 2024Article
- The Role of Alarmins in the Pathogenesis of Atherosclerosis and Myocardial Infarction.Current issues in molecular biology · 2024Review
- Biomechanics-mediated endocytosis in atherosclerosis.Frontiers in cardiovascular medicine · 2024Review
- PCSK9 activation promotes early atherosclerosis in a vascular microphysiological system.APL bioengineering · 2023Article
- DNA nanoparticles targeting FOXO4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts.Nanoscale advances · 2023Article
- The Greatly Under-Represented Role of Smooth Muscle Cells in Atherosclerosis.Current atherosclerosis reports · 2023Review
- Fabrication of a Dual-Targeted Liposome-Coated Mesoporous Silica Core-Shell Nanoassembly for Targeted Cancer Therapy.ACS omega · 2023Article
- Effects of early PCSK9 inhibitor application on inflammation levels and microcirculatory function after PCI in patients with NSTE-ACS.American journal of translational research · 2023Article
- Lipid Droplet-a New Target in Ischemic Heart Disease.Journal of cardiovascular translational research · 2022Review
- Cell surface nucleolin is a novel ADAMTS5 receptor mediating endothelial cell apoptosis.Cell death & disease · 2022Article
- Smooth Muscle Cell-Macrophage Interactions Leading to Foam Cell Formation in Atherosclerosis: Location, Location, Location.Frontiers in physiology · 2022Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveEnzyme-modified nonoxidized low-density lipoprotein (ELDL) is present in human atherosclerotic lesions. Our objective is to understand the mechanisms of ELDL uptake and its effects on vascular smooth muscle cells (SMC). APPROACH AND
resultsTransformation of murine aortic SMCs into foam cells in response to ELDL was analyzed. ELDL, but not acetylated or oxidized LDL, was potent in inducing SMC foam cell formation. Inhibitors of macropinocytosis (LY294002, wortmannin, amiloride) attenuated ELDL uptake. In contrast, inhibitors of receptor-mediated endocytosis (dynasore, sucrose) and inhibitor of caveolae-/lipid raft-mediated endocytosis (filipin) had no effect on ELDL uptake in SMC, suggesting that macropinocytosis is the main mechanism of ELDL uptake by SMC. Receptor for advanced glycation end products (RAGE) is not obligatory for ELDL-induced SMC foam cell formation, but primes SMC for the uptake of oxidized LDL in a RAGE-dependent manner. ELDL increased intracellular reactive oxygen species, cytosolic calcium, and expression of lectin-like oxidized LDL receptor-1 in wild-type SMC but not in RAGE(-/-) SMC. The macropinocytotic uptake of ELDL is regulated predominantly by intracellular calcium because ELDL uptake was completely inhibited by pretreatment with the calcium channel inhibitor lacidipine in wild-type and RAGE(-/-) SMC. This is in contrast to pretreatment with PI3 kinase inhibitors which completely prevented ELDL uptake in RAGE(-/-) SMC, but only partially in wild-type SMC.
conclusionsELDL is highly potent in inducing foam cells in murine SMC. ELDL endocytosis is mediated by calcium-dependent macropinocytosis. Priming SMC with ELDL enhances the uptake of oxidized LDL.
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