ArticleArteriosclerosis, thrombosis, and vascular biology2014
Scavenger receptor BI and high-density lipoprotein regulate thymocyte apoptosis in sepsis.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Precision Profiling of Disease Progression in Murine Models of Sepsis and Septic Shock.International journal of molecular sciences · 2025Article
- The Role of SR-BI in sepsis: leveraging mechanistic insights to advance precision steroid therapy.Frontiers in immunology · 2025Review
- Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Cell-Specific Immune Regulation by Glucocorticoids in Murine Models of Infection and Inflammation.Cells · 2022Review
- CircRNA CTNNB1 (circCTNNB1) ameliorates cerebral ischemia/reperfusion injury by sponging miR-96-5p to up-regulate scavenger receptor class B type 1 (SRB1) expression.Bioengineered · 2022Article
- Neuroimmune Regulation in Sepsis-Associated Encephalopathy: The Interaction Between the Brain and Peripheral Immunity.Frontiers in neurology · 2022Review
- High Free Cholesterol Bioavailability Drives the Tissue Pathologies in Scarb1Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Persistence of Lipoproteins and Cholesterol Alterations after Sepsis: Implication for Atherosclerosis Progression.International journal of molecular sciences · 2021Review
- Lipid and lipoprotein predictors of functional outcomes and long-term mortality after surgical sepsis.Annals of intensive care · 2021Article
- Lipid intensive drug therapy for sepsis pilot: A Bayesian phase I clinical trial.Journal of the American College of Emergency Physicians open · 2020Article
- Glucocorticoids in Sepsis: To Be or Not to Be.Frontiers in immunology · 2020Review
- Article
- SR-BI (Scavenger Receptor Class B Type 1) Is Critical in Maintaining Normal T-Cell Development and Enhancing Thymic Regeneration.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- HDL Cholesterol Efflux is Impaired in Older Patients with Early Sepsis: A Subanalysis of a Prospective Pilot Study.Shock (Augusta, Ga.) · 2018Article
- Protein markers of dysfunctional HDL in scavenger receptor class B type I deficient mice.Journal of translational medicine · 2018Article
- HDL inflammatory index correlates with and predicts severity of organ failure in patients with sepsis and septic shock.PloS one · 2018Observational
- Glucocorticoid Signaling in Health and Disease: Insights From Tissue-Specific GR Knockout Mice.Endocrinology · 2018Review
- Exploring the Predictive Ability of Dysfunctional High-Density Lipoprotein for Adverse Outcomes in Emergency Department Patients with Sepsis: A Preliminary Investigation.Shock (Augusta, Ga.) · 2017Article
- HDL-associated ApoM is anti-apoptotic by delivering sphingosine 1-phosphate to S1P1 & S1P3 receptors on vascular endothelium.Lipids in health and disease · 2017Article
- Corticosteroid Therapy Benefits Septic Mice With Adrenal Insufficiency But Harms Septic Mice Without Adrenal Insufficiency.Critical care medicine · 2015Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThymocyte apoptosis is a major event in sepsis; however, how this process is regulated remains poorly understood. APPROACH AND
resultsSeptic stress induces glucocorticoids production which triggers thymocyte apoptosis. Here, we used scavenger receptor BI (SR-BI)-null mice, which are completely deficient in inducible glucocorticoids in sepsis, to investigate the regulation of thymocyte apoptosis in sepsis. Cecal ligation and puncture induced profound thymocyte apoptosis in SR-BI(+/+) mice, but no thymocyte apoptosis in SR-BI(-/-) mice because of lack of inducible glucocorticoids. Unexpectedly, supplementation of glucocorticoids only partly restored thymocyte apoptosis in SR-BI(-/-) mice. We demonstrated that high-density lipoprotein (HDL) is a critical modulator for thymocyte apoptosis. SR-BI(+/+) HDL significantly enhanced glucocorticoid-induced thymocyte apoptosis, but SR-BI(-/-) HDL had no such activity. Further study revealed that SR-BI(+/+) HDL modulates glucocorticoid-induced thymocyte apoptosis via promoting glucocorticoid receptor translocation, but SR-BI(-/-) HDL loses such regulatory activity. To understand why SR-BI(-/-) HDL loses its regulatory activity, we analyzed HDL cholesterol contents. There was 3-fold enrichment of unesterified cholesterol in SR-BI(-/-) HDL compared with SR-BI(+/+) HDL. Normalization of unesterified cholesterol in SR-BI(-/-) HDL by probucol administration or lecithin cholesteryl acyltransferase expression restored glucocorticoid-induced thymocyte apoptosis, and incorporating unesterified cholesterol into SR-BI(+/+) HDL rendered SR-BI(+/+) HDL dysfunctional. Using lckCre-GR(fl/fl) mice in which thymocytes lack cecal ligation and puncture-induced thymocyte apoptosis, we showed that lckCre-GR(fl/fl) mice were significantly more susceptible to cecal ligation and puncture-induced septic death than GR(fl/fl) control mice, suggesting that glucocorticoid-induced thymocyte apoptosis is required for protection against sepsis.
conclusionsThe findings in this study reveal a novel regulatory mechanism of thymocyte apoptosis in sepsis by SR-BI and HDL.
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Registered trials
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