Evidence map›Paper›PMID 38660801›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2024

Mild Hypoxia Accelerates Cerebral Cavernous Malformation Disease Through CX3CR1-CX3CL1 Signaling.

Eduardo Frias-Anaya, Helios Gallego-Gutierrez, Brendan Gongol, Shantel Weinsheimer, Catherine Chinhchu Lai, Marco Orecchioni, Aditya Sriram, Cassandra M Bui, Bliss Nelsen, Preston Hale and 18 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
5.5field-weighted citation impact, top 3% of its field
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

15 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 7 institutions in 4 countries.

Eduardo Frias-AnayaDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.ORCID 0000-0003-2728-3648
Helios Gallego-GutierrezDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.ORCID 0000-0003-0369-9083
Brendan GongolDepartment of Health Sciences, Victor Valley College, Victorville, CA (B.G.).
Shantel WeinsheimerDepartment of Anesthesia and Perioperative Care, Institute for Human Genetics, University of California, San Francisco (S.W., A.S., H.K.).ORCID 0000-0001-7486-9110
Catherine Chinhchu LaiDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.
Marco OrecchioniDivision of Inflammation Biology, La Jolla Institute for Immunology, CA (M.O., K.L.).ORCID 0000-0002-3602-8510
Aditya SriramDepartment of Anesthesia and Perioperative Care, Institute for Human Genetics, University of California, San Francisco (S.W., A.S., H.K.).
Cassandra M BuiDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.
Bliss NelsenDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.ORCID 0000-0002-6183-1807
Preston HaleDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.
Angela PhamDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.
Robert ShenkarNeurovascular Surgery Program, Department of Neurological Surgery, The University of Chicago Medicine and Biological Sciences, IL (R.S., D.D., R.L., R.G., Y.L., A.S., I.A.A.).
Dorothy DeBiasseNeurovascular Surgery Program, Department of Neurological Surgery, The University of Chicago Medicine and Biological Sciences, IL (R.S., D.D., R.L., R.G., Y.L., A.S., I.A.A.).ORCID 0000-0002-4111-6750
Rhonda LightleNeurovascular Surgery Program, Department of Neurological Surgery, The University of Chicago Medicine and Biological Sciences, IL (R.S., D.D., R.L., R.G., Y.L., A.S., I.A.A.).ORCID 0000-0003-2760-195X
Romuald GirardNeurovascular Surgery Program, Department of Neurological Surgery, The University of Chicago Medicine and Biological Sciences, IL (R.S., D.D., R.L., R.G., Y.L., A.S., I.A.A.).
Ying LiNeurovascular Surgery Program, Department of Neurological Surgery, The University of Chicago Medicine and Biological Sciences, IL (R.S., D.D., R.L., R.G., Y.L., A.S., I.A.A.).ORCID 0000-0002-4107-5442
Abhinav SrinathNeurovascular Surgery Program, Department of Neurological Surgery, The University of Chicago Medicine and Biological Sciences, IL (R.S., D.D., R.L., R.G., Y.L., A.S., I.A.A.).
Richard DanemanDepartment of Pharmacology (R.D., M.A.L.-R.), University of California San Diego, La Jolla.
Eric NudlemanDepartment of Ophthalmology (E.N.), University of California San Diego, La Jolla.
Hao SunDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.ORCID 0000-0002-4790-8847
Monica GumaDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.ORCID 0000-0003-1951-9411
Alexandre DubracCentre de Recherche, CHU St. Justine, Montréal, Quebec, Canada. Département de Pathologie et Biologie Cellulaire, Université de Montréal, Quebec, Canada (A.D.).ORCID 0000-0002-3829-2577
Omar A MesarwiDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.ORCID 0000-0003-3102-6468
Klaus LeyDivision of Inflammation Biology, La Jolla Institute for Immunology, CA (M.O., K.L.).ORCID 0000-0001-9339-3672
Helen KimDepartment of Anesthesia and Perioperative Care, Institute for Human Genetics, University of California, San Francisco (S.W., A.S., H.K.).ORCID 0000-0002-1937-354X
Issam A AwadNeurovascular Surgery Program, Department of Neurological Surgery, The University of Chicago Medicine and Biological Sciences, IL (R.S., D.D., R.L., R.G., Y.L., A.S., I.A.A.).ORCID 0000-0003-1510-602X
Mark H GinsbergDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.
Miguel Alejandro Lopez-RamirezDepartment of Medicine (E.F.-A., H.G.-G., C.C.L., C.M.B., B.N., P.H., A.P., H.S., M.G., O.A.M., M.H.G., M.A.L.-R.), University of California San Diego, La Jolla.ORCID 0000-0001-7089-4060
University of California San Diego · USNeurological Surgery · USInstitute of Human Genetics · PLLa Jolla Institute for Immunology · USAnna Needs Neuroblastoma Answers · USCentre Hospitalier Universitaire Sainte-Justine · CAUniversity of California, Riverside · US

Funding

VCRC Administration UnitU54NS065705 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KIM, HELEN · 2009 to 2023
$20.8M
The Hemostasis, Thrombosis, and Inflammation Models CoreP01HL151433 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Mark HOWARD Ginsberg · 2020 to 2026
$16.4M
Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant (Parent T32)T32HD007009 · NICHD · UNIVERSITY OF CHICAGO · PI NANCY B SCHWARTZ · 1985 to 2026
$13.0M
Somatic mutation(s) and cellular changes in CCM pathogenesisP01NS092521 · NINDS · DUKE UNIVERSITY · PI MARCHUK, DOUGLAS A. · 2015 to 2024
$12.9M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Mechanisms of hypoxia induced exacerbation of cerebral cavernous malformationsR01NS121070 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Miguel Alejandro Lopez-Ramirez · 2022 to 2026
$2.3M
Regulation of endothelial gene expression by cerebral cavernous malformation complexK01HL133530 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOPEZ-RAMIREZ, MIGUEL ALEJANDRO · 2018 to 2022
$903k
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
American Heart Association-American Stroke Association 941152NHLBI NIH HHS K01 HL133530NHLBI NIH HHS P01 HL151433NICHD NIH HHS T32 HD007009NIH HHS S10 OD026929NINDS NIH HHS P01 NS092521NINDS NIH HHS P30 NS047101NINDS NIH HHS R01 NS121070NINDS NIH HHS U54 NS065705
6 · The paper itself

Abstract

backgroundHeterogeneity in the severity of cerebral cavernous malformations (CCMs) disease, including brain bleedings and thrombosis that cause neurological disabilities in patients, suggests that environmental, genetic, or biological factors act as disease modifiers. Still, the underlying mechanisms are not entirely understood. Here, we report that mild hypoxia accelerates CCM disease by promoting angiogenesis, neuroinflammation, and vascular thrombosis in the brains of CCM mouse models.

methodsWe used genetic studies, RNA sequencing, spatial transcriptome, micro-computed tomography, fluorescence-activated cell sorting, multiplex immunofluorescence, coculture studies, and imaging techniques to reveal that sustained mild hypoxia via the CX3CR1-CX3CL1 (CX3C motif chemokine receptor 1/chemokine [CX3C motif] ligand 1) signaling pathway influences cell-specific neuroinflammatory interactions, contributing to heterogeneity in CCM severity.

resultsHistological and expression profiles of CCM neurovascular lesions (

conclusionsOur study reveals that interactions between CX3CR1 and CX3CL1 can modify CCM neuropathology when lesions are accelerated by environmental hypoxia. Moreover, a hypoxic environment or hypoxia signaling caused by CCM disease influences the balance between neuroinflammation and neuroprotection mediated by CX3CR1-CX3CL1 signaling. These results establish

Indexed as

Chemokine CX3CL1CX3C Chemokine Receptor 1Disease Models, AnimalHemangioma, Cavernous, Central Nervous SystemSignal TransductionAnimalsFemaleHumansHypoxiaMaleMiceMice, Inbred C57BLMice, KnockoutNeovascularization, PathologicNeuroinflammatory DiseasesChemokine CX3CL1CX3C Chemokine Receptor 1CX3CL1 protein, humanCx3cl1 protein, mouseCX3CR1 protein, humanCx3cr1 protein, mousegenetic markershemangioma, cavernous, central nervous systemhypoxianeuroinflammatory diseasesthromboinflammation

Identifiers

PMID38660801
PMCPMC11111348
OpenAlexW4395463617

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.