ArticlePloS one2016
Rapamycin Inhibits Oxidized Low Density Lipoprotein Uptake in Human Umbilical Vein Endothelial Cells via mTOR/NF-κB/LOX-1 Pathway.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Immunosuppression Drugs Exhibit Differential Effects on Endothelial Cell Function.Journal of vascular research · 2026Article
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- Oxidized LDL Accelerates Cartilage Destruction and Inflammatory Chondrocyte Death in Osteoarthritis by Disrupting the TFEB-Regulated Autophagy-Lysosome Pathway.Immune network · 2024Article
- The Effects of Sirolimus and Magnesium on Primary Human Coronary Endothelial Cells: An In Vitro Study.International journal of molecular sciences · 2023Article
- New insight into dyslipidemia-induced cellular senescence in atherosclerosis.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Relationship between Brain Metabolic Disorders and Cognitive Impairment: LDL Receptor Defect.International journal of molecular sciences · 2022Review
- Cardiovascular effects of immunosuppression agents.Frontiers in cardiovascular medicine · 2022Review
- Impaired lipophagy in endothelial cells with prolonged exposure to oxidized low‑density lipoprotein.Molecular medicine reports · 2020Article
- Chaiqi decoction ameliorates vascular endothelial injury in metabolic syndrome by upregulating autophagy.American journal of translational research · 2020Article
- LOX-1: Regulation, Signaling and Its Role in Atherosclerosis.Antioxidants (Basel, Switzerland) · 2019Review
- Downregulation of GATA6 in mTOR-inhibited human aortic endothelial cells: effects on TNF-α-induced VCAM-1 expression and monocytic cell adhesion.American journal of physiology. Heart and circulatory physiology · 2019Article
- Rapamycin Attenuates High Glucose-Induced Inflammation Through Modulation of mTOR/NF-κB Pathways in Macrophages.Frontiers in pharmacology · 2019Article
- Inhibition of mTOR protects the blood-brain barrier in models of Alzheimer's disease and vascular cognitive impairment.American journal of physiology. Heart and circulatory physiology · 2018Article
- Oxidized low-density lipoprotein stimulates epithelial sodium channels in endothelial cells of mouse thoracic aorta.British journal of pharmacology · 2018Article
- Article
- Rapamycin: A Bacteria-Derived Immunosuppressant That Has Anti-atherosclerotic Effects and Its Clinical Application.Frontiers in pharmacology · 2018Review
- Rapamycin Inhibits Cardiac Hypertrophy by Promoting Autophagy via the MEK/ERK/Beclin-1 Pathway.Frontiers in physiology · 2016Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLectin-like oxidized low-density lipoprotein-1 (LOX-1) is the major receptor for oxidized low density lipoprotein (ox-LDL) uptake in human umbilical vein endothelial cells (HUVECs). Previously, we found that rapamycin inhibited ox-LDL accumulation in HUVECs, and this effect was related to its role in increasing the activity of autophagy-lysosome pathway. In this study, we determined whether rapamycin could also reduce ox-LDL uptake in HUVECs and investigated the underlying signaling mechanisms.
resultsFlow cytometry and live cell imaging showed that rapamycin reduced Dil-ox-LDL accumulation in HUVECs. Furthermore, rapamycin reduced the ox-LDL-induced increase in LOX-1 mRNA and protein levels. Western blotting showed that rapamycin inhibited mechanistic target of rapamycin (mTOR), p70s6k and IκBα phosphorylation triggered by ox-LDL. Flow cytometry implied that mTOR, NF-κB knockdown and NF-κB inhibitors significantly reduced Dil-ox-LDL uptake. Moreover, immunofluorescent staining showed that rapamycin reduced the accumulation of p65 in the nucleus after ox-LDL treatment for 30 h. mTOR knockdown decreased LOX-1 protein production and IκBα phosphorylation induced by ox-LDL. NF-κB knockdown and NF-κB inhibitors reduced LOX-1 protein production, but did not inhibit mTOR phosphorylation stimulated by ox-LDL.
conclusionsThese findings demonstrate that rapamycin reduce mTOR phosphorylation and subsequently inhibit NF-κB activation and suppresses LOX-1, resulting in a reduction in ox-LDL uptake in HUVECs.
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