ArticleArteriosclerosis, thrombosis, and vascular biology2019
Dynamic Actin Reorganization and Vav/Cdc42-Dependent Actin Polymerization Promote Macrophage Aggregated LDL (Low-Density Lipoprotein) Uptake and Catabolism.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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
28 citing papers in PubMed, 38 citations in OpenAlex.
- Toll-like receptor 4 signaling links cytoskeletal remodeling to lipid accumulation in macrophages.Inflammation and regeneration · 2026Review
- Microglial tunneling nanotubes: an intercellular transfer facilitating mitochondrial dysfunction and neuroinflammation in experimental cerebral malaria.Apoptosis : an international journal on programmed cell death · 2026Article
- Protocol for the quantification of digestive exophagy in cell culture.STAR protocols · 2026Article
- The LDL pathway regulates actomyosin ring dynamics necessary for optimal cell wound repair.microPublication biology · 2026Article
- ToF-SIMS Imaging for the Analysis of Cholesterol Formation at Macrophage Membrane.Metabolites · 2025Article
- High-Content Microscopy Drug Screening Platform for Regulators of the Extracellular Digestion of Lipoprotein Aggregates by Macrophages.ACS pharmacology & translational science · 2025Article
- Identification of shared mechanisms between Alzheimer's disease and atherosclerosis by integrated bioinformatics analysis.European journal of medical research · 2025Article
- Unraveling the proteomic signatures of coronary artery disease and hypercholesterolemia.Biomolecules & biomedicine · 2025Article
- Microglia degrade Alzheimer's amyloid-beta deposits extracellularly via digestive exophagy.Cell reports · 2024Article
- Vav family exchange factors: Potential regulator in atherosclerosis.Biochemistry and biophysics reports · 2024Review
- Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization.Frontiers in cardiovascular medicine · 2024Article
- Signaling pathways regulating the extracellular digestion of lipoprotein aggregates by macrophages.Molecular biology of the cell · 2024Article
- Biomechanics-mediated endocytosis in atherosclerosis.Frontiers in cardiovascular medicine · 2024Review
- Hypofucosylation of Unc5b regulated by Fut8 enhances macrophage emigration and prevents atherosclerosis.Cell & bioscience · 2023Article
- Morphological Evidence for Novel Roles of Microtubules in Macrophage Phagocytosis.International journal of molecular sciences · 2023Article
- The formation and consequences of cholesterol-rich deposits in atherosclerotic lesions.Frontiers in cardiovascular medicine · 2023Review
- Vav Proteins in Development of the Brain: A Potential Relationship to the Pathogenesis of Congenital Zika Syndrome?Viruses · 2022Review
- Longitudinal Variations of CDC42 in Patients With Acute Ischemic Stroke During 3-Year Period: Correlation With CD4Frontiers in neurology · 2022Article
- Aggregation Susceptibility of Low-Density Lipoproteins-A Novel Modifiable Biomarker of Cardiovascular Risk.Journal of clinical medicine · 2021Review
- The Emerging Role of Rho Guanine Nucleotide Exchange Factors in Cardiovascular Disorders: Insights Into Atherosclerosis: A Mini Review.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Objective- During atherosclerosis, LDLs (low-density lipoproteins) accumulate in the arteries, where they become modified, aggregated, and retained. Such deposits of aggregated LDL (agLDL) can be recognized by macrophages, which attempt to digest and clear them. AgLDL catabolism promotes internalization of cholesterol and foam cell formation, which leads to the progression of atherosclerosis. Therapeutic blockade of this process may delay disease progression. When macrophages interact with agLDL in vitro, they form a novel extracellular, hydrolytic compartment-the lysosomal synapse (LS)-aided by local actin polymerization to digest agLDL. Here, we investigated the specific regulators involved in actin polymerization during the formation of the LS. Approach and Results- We demonstrate in vivo that atherosclerotic plaque macrophages contacting agLDL deposits polymerize actin and form a compartment strikingly similar to those made in vitro. Live cell imaging revealed that macrophage cortical F-actin depolymerization is required for actin polymerization to support the formation of the LS. This depolymerization is cofilin-1 dependent. Using siRNA-mediated silencing, pharmacological inhibition, genetic knockout, and stable overexpression, we elucidate key roles for Cdc42 Rho GTPase and GEF (guanine nucleotide exchange factor) Vav in promoting actin polymerization during the formation of the LS and exclude a role for Rac1. Conclusions- These results highlight critical roles for dynamic macrophage F-actin rearrangement and polymerization via cofilin-1, Vav, and Cdc42 in LS formation, catabolism of agLDL, and foam cell formation. These proteins might represent therapeutic targets to treat atherosclerotic disease.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.