ArticleThe Journal of clinical investigation2021
Macrophage SR-BI modulates autophagy via VPS34 complex and PPARα transcription of Tfeb in atherosclerosis.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Macrophage Subsets and Death Are Responsible for Atherosclerotic Plaque Formation.Frontiers in immunology · 2022Pooled it
- Sulfhydrated TFEB alleviates blast-induced lung injury by maintaining epithelial barrier integrity through the IGF2R/MMP-2/9 pathway.Redox biology · 2026Article
- Jingling Granules alleviate atherosclerosis through activating autophagy and inhibiting human umbilical vein endothelial cells apoptosis.Scientific reports · 2026Article
- Lactate-mediated cholesterol uptake promotes liver cancer progression via the SCARB1-autophagy axis.EMBO reports · 2026Article
- Microvascular endothelial scavenger receptor class B type I protects against heart failure with preserved ejection fraction by inhibiting T-cell cardiotropism.EMBO molecular medicine · 2026Article
- Distinct types of regulated cell death in atherosclerosis.Journal of pharmaceutical analysis · 2026Review
- Ring finger protein 213 regulates B-cell receptor signaling, metabolism, and development in B lymphocytes.Signal transduction and targeted therapy · 2026Article
- Research progress on targeted regulatory proteins in the prevention and treatment of atherosclerosis.Frontiers in immunology · 2026Review
- Foam cells: tracing the diverse cellular origins and their linked signaling pathways.Journal of translational medicine · 2025Review
- Recent insights into the pathophysiology and implications for surgery in atherosclerosis.Journal of cardiothoracic surgery · 2025Review
- Ablation of Mouse Selenium-Binding Protein 1 and 2 Elevates LDL by Disruption of Cholesterol Efflux and Lipid Metabolism.International journal of molecular sciences · 2025Article
- Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis.International journal of molecular sciences · 2025Review
- Lysosomes in the immunometabolic reprogramming of immune cells in atherosclerosis.Nature reviews. Cardiology · 2025Review
- Deletion of the scavenger receptor Scarb1 in osteoblast progenitors and myeloid cells does not affect bone mass.PloS one · 2025Article
- Functional interaction between immune checkpoints and lipid metabolism in the development of arteriosclerosis obliterans.Frontiers in immunology · 2025Review
- Study on the anti-atherosclerosis mechanisms of Tanyu Tongzhi formula based on network pharmacology, Mendelian randomization, and experimental verification.Pharmaceutical biology · 2024Article
- Inflammation in atherosclerosis: pathophysiology and mechanisms.Cell death & disease · 2024Review
- Vps34 sustains Treg cell survival and function via regulating intracellular redox homeostasis.Cell death and differentiation · 2024Article
- Regulatory Mechanisms Governing the Autophagy-Initiating VPS34 Complex and Its inhibitors.Biomolecules & therapeutics · 2024Review
- Associations of the PPARα and Lipoprotein Lipase Enzyme Gene Polymorphisms with Dyslipidemia in Obese and Non-obese Males.Journal of obesity & metabolic syndrome · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
Abstract
Autophagy modulates lipid turnover, cell survival, inflammation, and atherogenesis. Scavenger receptor class B type I (SR-BI) plays a crucial role in lysosome function. Here, we demonstrate that SR-BI regulates autophagy in atherosclerosis. SR-BI deletion attenuated lipid-induced expression of autophagy mediators in macrophages and atherosclerotic aortas. Consequently, SR-BI deletion resulted in 1.8- and 2.5-fold increases in foam cell formation and apoptosis, respectively, and increased oxidized LDL-induced inflammatory cytokine expression. Pharmacological activation of autophagy failed to reduce lipid content or apoptosis in Sr-b1-/- macrophages. SR-BI deletion reduced both basal and inducible levels of transcription factor EB (TFEB), a master regulator of autophagy, causing decreased expression of autophagy genes encoding VPS34 and Beclin-1. Notably, SR-BI regulated Tfeb expression by enhancing PPARα activation. Moreover, intracellular macrophage SR-BI localized to autophagosomes, where it formed cholesterol domains resulting in enhanced association of Barkor and recruitment of the VPS34-Beclin-1 complex. Thus, SR-BI deficiency led to lower VPS34 activity in macrophages and in atherosclerotic aortic tissues. Overexpression of Tfeb or Vps34 rescued the defective autophagy in Sr-b1-/- macrophages. Taken together, our results show that macrophage SR-BI regulates autophagy via Tfeb expression and recruitment of the VPS34-Beclin-1 complex, thus identifying previously unrecognized roles for SR-BI and potentially novel targets for the treatment of atherosclerosis.
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