ArticleEuropean heart journal2020
Glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR) drives atherosclerosis in mice and is associated with an unstable plaque phenotype and cerebrovascular events in humans.
Article in European heart journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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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.
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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.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 37 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Progress in aorta and peripheral cardiovascular disease research.Cardiovascular research · 2021Pooled it
- Reversing the pipeline: a 'human-first' multi-omics approach to cardiovascular discovery.Experimental & molecular medicine · 2026Review
- LIGHT/TNFSF14 Levels in Carotid Plaques Are Associated With Symptomatic Cerebrovascular Disease.Journal of stroke · 2025Article
- TNF superfamily molecules in atherosclerosis: mechanistic insights and therapeutic translation.Frontiers in immunology · 2025Review
- Immune Checkpoints Are New Therapeutic Targets in Regulating Cardio-, and Cerebro-Vascular Diseases and CD4International journal of drug discovery and pharmacology · 2024Article
- Immune checkpoint landscape of human atherosclerosis and influence of cardiometabolic factors.Nature cardiovascular research · 2024Article
- Article
- Genetic factors in the pathogenesis of cardio-oncology.Journal of translational medicine · 2024Review
- Peritoneal Dialysis Aggravates and Accelerates Atherosclerosis in UremicJournal of the American Heart Association · 2024Article
- Immune checkpoints in cardiac physiology and pathology: therapeutic targets for heart failure.Nature reviews. Cardiology · 2024Review
- T-Cell/B-Cell Interactions in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- GITR exacerbates lysophosphatidylcholine-induced macrophage pyroptosis in sepsis via posttranslational regulation of NLRP3.Cellular & molecular immunology · 2024Article
- Costimulatory and Coinhibitory Immune Checkpoints in Atherosclerosis: Therapeutic Targets in Atherosclerosis?JACC. Basic to translational science · 2024Review
- Gegen Qinlian Decoction Modulates Atherosclerosis and Lipid Metabolism Through Cellular Interplay and Signaling Pathways.Combinatorial chemistry & high throughput screening · 2024Article
- Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages' transition into a pro-inflammatory state.Cardiovascular research · 2023Article
- Atherosclerosis With Immune Checkpoint Inhibitor Therapy: Evidence, Diagnosis, and Management:JACC. CardioOncology · 2022Review
- Article
- Microvesicles released from activated CD4European journal of clinical investigation · 2022Article
- Prime-seq, efficient and powerful bulk RNA sequencing.Genome biology · 2022Article
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Authors and funding
24 authors at 9 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsGITR-a co-stimulatory immune checkpoint protein-is known for both its activating and regulating effects on T-cells. As atherosclerosis bears features of chronic inflammation and autoimmunity, we investigated the relevance of GITR in cardiovascular disease (CVD). METHODS AND
resultsGITR expression was elevated in carotid endarterectomy specimens obtained from patients with cerebrovascular events (n = 100) compared to asymptomatic patients (n = 93) and correlated with parameters of plaque vulnerability, including plaque macrophage, lipid and glycophorin A content, and levels of interleukin (IL)-6, IL-12, and C-C-chemokine ligand 2. Soluble GITR levels were elevated in plasma from subjects with CVD compared to healthy controls. Plaque area in 28-week-old Gitr-/-Apoe-/- mice was reduced, and plaques had a favourable phenotype with less macrophages, a smaller necrotic core and a thicker fibrous cap. GITR deficiency did not affect the lymphoid population. RNA sequencing of Gitr-/-Apoe-/- and Apoe-/- monocytes and macrophages revealed altered pathways of cell migration, activation, and mitochondrial function. Indeed, Gitr-/-Apoe-/- monocytes displayed decreased integrin levels, reduced recruitment to endothelium, and produced less reactive oxygen species. Likewise, GITR-deficient macrophages produced less cytokines and had a reduced migratory capacity.
conclusionOur data reveal a novel role for the immune checkpoint GITR in driving myeloid cell recruitment and activation in atherosclerosis, thereby inducing plaque growth and vulnerability. In humans, elevated GITR expression in carotid plaques is associated with a vulnerable plaque phenotype and adverse cerebrovascular events. GITR has the potential to become a novel therapeutic target in atherosclerosis as it reduces myeloid cell recruitment to the arterial wall and impedes atherosclerosis progression.
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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.