ArticleScience signaling2016
Inclusion bodies enriched for p62 and polyubiquitinated proteins in macrophages protect against atherosclerosis.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- The Heart of the Alzheimer's: A Mindful View of Heart Disease.Frontiers in physiology · 2020Pooled it
- Sex differences in human umbilical vein endothelial cells following ox-LDL injury.Biology of sex differences · 2026Article
- Inhibition of CD36 ameliorates mouse spinal cord injury by accelerating microglial lipophagy.Acta pharmacologica Sinica · 2025Article
- Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis.International journal of molecular sciences · 2025Review
- Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.Biomolecules · 2025Review
- NLRP3 inflammasome in cardiovascular diseases: an update.Frontiers in immunology · 2025Review
- Antiatherogenic and Cardioprotective Effects of a Xanthine Derivative KMUP-1 in ApoE Knockout Mice.Cardiovascular therapeutics · 2025Article
- Regulation and Functions of Autophagy During Animal Development.Journal of molecular biology · 2024Review
- Elucidating the crosstalk between endothelial-to-mesenchymal transition (EndoMT) and endothelial autophagy in the pathogenesis of atherosclerosis.Vascular pharmacology · 2024Review
- The crosstalk between mitochondrial quality control and metal-dependent cell death.Cell death & disease · 2024Review
- Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease.Cells · 2024Review
- Endothelium-specific deletion of p62 causes organ fibrosis and cardiac dysfunction.Journal of translational medicine · 2024Article
- Trehalose promotes atherosclerosis regression in female mice.Frontiers in cardiovascular medicine · 2024Article
- Itaconate suppresses atherosclerosis by activating a Nrf2-dependent antiinflammatory response in macrophages in mice.The Journal of clinical investigation · 2023Article
- Measurement of SQSTM1 by flow cytometry.Autophagy · 2023Article
- Inhibition of pro-inflammatory signaling in human primary macrophages by enhancing arginase-2 via target site blockers.Molecular therapy. Nucleic acids · 2023Article
- Genetic inhibition of CARD9 accelerates the development of atherosclerosis in mice through CD36 dependent-defective autophagy.Nature communications · 2023Article
- Use of acidic nanoparticles to rescue macrophage lysosomal dysfunction in atherosclerosis.Autophagy · 2023Article
- Mitochondrial quality control in health and cardiovascular diseases.Frontiers in cell and developmental biology · 2023Review
- Autophagy in Atherosclerotic Plaque Cells: Targeting NLRP3 Inflammasome for Self-Rescue.Biomolecules · 2022Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Autophagy is a catabolic cellular mechanism that degrades dysfunctional proteins and organelles. Atherosclerotic plaque formation is enhanced in mice with macrophages deficient for the critical autophagy protein ATG5. We showed that exposure of macrophages to lipids that promote atherosclerosis increased the abundance of the autophagy chaperone p62 and that p62 colocalized with polyubiquitinated proteins in cytoplasmic inclusions, which are characterized by insoluble protein aggregates. ATG5-null macrophages developed further p62 accumulation at the sites of large cytoplasmic ubiquitin-positive inclusion bodies. Aortas from atherosclerotic mice and plaques from human endarterectomy samples showed increased abundance of p62 and polyubiquitinated proteins that colocalized with plaque macrophages, suggesting that p62-enriched protein aggregates were characteristic of atherosclerosis. The formation of the cytoplasmic inclusions depended on p62 because lipid-loaded p62-null macrophages accumulated polyubiquitinated proteins in a diffuse cytoplasmic pattern. Lipid-loaded p62-null macrophages also exhibited increased secretion of interleukin-1β (IL-1β) and had an increased tendency to undergo apoptosis, which depended on the p62 ubiquitin-binding domain and at least partly involved p62-mediated clearance of NLRP3 inflammasomes. Consistent with our in vitro observations, p62-deficient mice formed greater numbers of more complex atherosclerotic plaques, and p62 deficiency further increased atherosclerotic plaque burden in mice with a macrophage-specific ablation of ATG5. Together, these data suggested that sequestration of cytotoxic ubiquitinated proteins by p62 protects against atherogenesis, a condition in which the clearance of protein aggregates is disrupted.
Indexed as
Identifiers
What Socratic holds
Registered trials
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 Socratic graph.