Evidence map›Paper›PMID 42849439›Full record

ArticleCell2026

Immunoregulatory gene GIMAP6 suppresses lethal atherosclerotic vasculopathy and ischemic heart failure.

Chen Xiang, Kaja Arusha, Danielle Springer, Sachiko Nakamori, Jing Cui, Ping Du Jiang, Zhi-Hong Yang, Yu Zhang, Huie Jing, Ann Y Park and 25 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors.

Chen XiangMolecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID/NIH, Bethesda, MD, USA; Human Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA.
Kaja ArushaHuman Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA.
Danielle SpringerMurine Phenotyping Core, NHLBI/NIH, Bethesda, MD, USA.
Sachiko NakamoriMurine Phenotyping Core, NHLBI/NIH, Bethesda, MD, USA.
Jing CuiMolecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA; Calico Life Sciences LLC, South San Francisco, CA, USA.
Ping Du JiangMolecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA.
Zhi-Hong YangLipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, NHLBI/NIH, Bethesda, MD, USA.
Yu ZhangHuman Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA.
Huie JingHuman Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA.
Ann Y ParkMolecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA.
Maria H ZhuMolecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA.
Sarah E WeberMolecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA.
Deniz CagdasPediatric Immunology, Department of Pediatrics, Hacettepe University Medical School, Ankara, Turkey; Immunology, Pediatric Basic Sciences, Child Health Institute, Hacettepe University, Ankara, Turkey.
Hassan AbolhassaniResearch Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Clinic for Pediatric Immunology and Rheumatology, University Hospital Bonn, Bonn, Germany.
Nasrin BehniafardChildren Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Margery G SmelkinsonBiological Imaging Section, Research Technologies Branch, NIAID/NIH, Bethesda, MD, USA.
Qihui LiangLaboratory of Biochemistry and Molecular Biology, NCI/NIH, Bethesda, MD, USA.
Elif EverestTranslational Neuroradiology Section, NINDS/NIH, Bethesda, MD, USA.
Julia F KunLipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, NHLBI/NIH, Bethesda, MD, USA.
Alyssa GroganCVPath Institute Inc., Gaithersburg, MD, USA.
Bernd J WranikCalico Life Sciences LLC, South San Francisco, CA, USA.
Ngoc VuCalico Life Sciences LLC, South San Francisco, CA, USA.
Bryan KingCalico Life Sciences LLC, South San Francisco, CA, USA.
Jennifer D TreatImmunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology, NIAID/NIH, Bethesda, MD, USA.
Nancy AsomaningLaboratory of Sickle Cell Genetics and Pathophysiology, NHLBI/NIH, Bethesda, MD, USA.
Shijinqiu GaoLaboratory of Sickle Cell Genetics and Pathophysiology, NHLBI/NIH, Bethesda, MD, USA.
Bryson D BennettCalico Life Sciences LLC, South San Francisco, CA, USA.
Swee Lay TheinLaboratory of Sickle Cell Genetics and Pathophysiology, NHLBI/NIH, Bethesda, MD, USA.
Christa S ZerbeClinical Genomics Program, NIAID/NIH, Bethesda, MD, USA; Immunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology, NIAID/NIH, Bethesda, MD, USA.
Steven M HollandClinical Genomics Program, NIAID/NIH, Bethesda, MD, USA; Immunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology, NIAID/NIH, Bethesda, MD, USA.
Renu VirmaniCVPath Institute Inc., Gaithersburg, MD, USA.
Alan T RemaleyLipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, NHLBI/NIH, Bethesda, MD, USA.
Helen C SuHuman Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA.
Lixin ZhengMolecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA; Calico Life Sciences LLC, South San Francisco, CA, USA.
Michael J LenardoMolecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID/NIH, Bethesda, MD, USA; Clinical Genomics Program, NIAID/NIH, Bethesda, MD, USA; Calico Life Sciences LLC, South San Francisco, CA, USA. Electronic address: lenardo@calicolabs.com.

Funding

GENE REGULATORY EVENTS IN ESTABLISHING MATURE T CELL TOLERANCEZIAAI000566 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN CHUN-HUI · 2009 to 2025
$11.4M
Intramural NIH HHS ZIA AI000566
6 · The paper itself

Abstract

Controlling hyperlipidemia has reduced but not eliminated atherosclerotic cardiovascular disease (ASCVD) as a major cause of human mortality. Here, we report that loss of the immunoregulatory gene GTPase of immunity-associated protein 6 (Gimap6) in mice causes an inflammatory vasculopathy and accelerated atherosclerosis in the absence of hyperlipidemia. These vascular abnormalities cause progressive cardiac ischemia, myocardial infarction, and heart failure, culminating in early death. GIMAP6 loss precipitates early endothelial barrier failure and a mitochondrial reactive oxygen species (ROS)-PPARγ-CD36 lipid-influx cascade that lowers the threshold for foam-cell formation and induces IL-6/MCP-1/TNF-mediated inflammation. Human hypomorphic GIMAP6 variants, including the African-ancestry-enriched V65I allele, are associated with altered monocyte redox balance, increased CD36-mediated lipid uptake, and early ASCVD. Thus, GIMAP6 is a crucial safeguard for vascular integrity that restrains endothelial dysfunction, macrophage foam cell generation, and inflammation that can cause lethal ASCVD independently of systemic hyperlipidemia.

Indexed as

AtherosclerosisHeart FailureMyocardial IschemiaAnimalsCD36 AntigensFoam CellsHumansHyperlipidemiasInflammationMaleMiceMice, Inbred C57BLMice, KnockoutMitochondriaPPAR gammaReactive Oxygen SpeciesCD36 AntigensPPAR gammaReactive Oxygen SpeciescardiovascularCD36endotheliumlipidmacrophagemitochondriamyocardial infarctionredox

Identifiers

PMID42849439
PMCPMC13688317

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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.