ArticleProceedings of the National Academy of Sciences of the United States of America2014
Endothelial cellular senescence is inhibited by liver X receptor activation with an additional mechanism for its atheroprotection in diabetes.
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 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
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- Mapping the research trends and hotspots in vascular aging from 2003-2023: A bibliometric analysis.Heliyon · 2024Article
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- Prognostic Significance and Biologic Associations of Senescence-Associated Secretory Phenotype Biomarkers in Heart Failure.Journal of the American Heart Association · 2024Article
- Increased Prolylcarboxypeptidase Expression Can Serve as a Biomarker of Senescence in Culture.Molecules (Basel, Switzerland) · 2024Article
- Inhibition of mammalian target of rapamycin complex 1 in the brain microvascular endothelium ameliorates diabetic Aβ brain deposition and cognitive impairment via the sterol-regulatory element-binding protein 1/lipoprotein receptor-associated protein 1 signaling pathway.CNS neuroscience & therapeutics · 2023Article
- Roles of TSP1-CD47 signaling pathway in senescence of endothelial cells: cell cycle, inflammation and metabolism.Molecular biology reports · 2023Review
- Diabetes and Its Cardiovascular Complications: Potential Role of the Acetyltransferase p300.Cells · 2023Review
- Mechanisms and consequences of endothelial cell senescence.Nature reviews. Cardiology · 2023Review
- Targeting macrophages in atherosclerosis using nanocarriers loaded with liver X receptor agonists: A narrow review.Frontiers in molecular biosciences · 2023Review
- Global research trends in atherosclerosis: A bibliometric and visualized study.Frontiers in cardiovascular medicine · 2022Article
- A validated analysis pipeline for mass spectrometry-based vitreous proteomics: new insights into proliferative diabetic retinopathy.Clinical proteomics · 2021Article
- Combined LXR and RXR Agonist Therapy Increases ABCA1 Protein Expression and Enhances ApoAI-Mediated Cholesterol Efflux in Cultured Endothelial Cells.Metabolites · 2021Article
- Endothelial cells from umbilical cord of women affected by gestational diabetes: A suitable in vitro model to study mechanisms of early vascular senescence in diabetes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Senescence of vascular endothelial cells leads to endothelial dysfunction and contributes to the progression of atherosclerosis. Liver X receptors (LXRs) are nuclear receptors whose activation protects against atherosclerosis by transcriptional regulation of genes important in promoting cholesterol efflux and inhibiting inflammation. Here we found that LXR activation with specific ligands reduced the increase in senescence-associated (SA) β-gal activity, a senescence marker, and reversed the decrease in telomerase activity, a replicative senescence marker, in human endothelial cells under high glucose. This effect of LXR activation was associated with reduced reactive oxygen species and increased endothelial NO synthase activity. A series of experiments that used siRNAs indicated that LXRβ mediates the prevention of endothelial cellular senescence, and that sterol regulatory element binding protein-1, which was up-regulated as a direct LXRβ target gene, may act as a brake of endothelial cellular senescence. Although oral administration of the LXR ligand led to severe fatty liver in diabetic rats, concomitant therapy with metformin avoided the development of hepatic steatosis. However, the preventive effect of the LXR ligand on SA β-gal-stained cells in diabetic aortic endothelium was preserved even if metformin was coadministered. Taken together, our studies demonstrate that an additional mechanism, such as the regulation of endothelial cellular senescence, is related to the antiatherogenic properties of LXRs, and concomitant treatment with metformin may provide a clinically useful therapeutic strategy to alleviate an LXR activation-mediated adverse effects on liver triglyceride metabolism.
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