Evidence map›Paper›PMID 40336480›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2025

Impaired CAMK4 Activity Limits Atherosclerosis and Reprograms Myelopoiesis.

Azuah L Gonzalez, Cristina M Youwakim, Brenda F Leake, Kristin K Fuller, S M Jamshedur Rahman, Matthew M Dungan, Katherine Gu, Jesse L Bonin, Ashley B Cavnar, Danielle L Michell and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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

25 authors.

Azuah L GonzalezDepartment of Pathology, Microbiology, and Immunology (A.L.G., M.M.D., A.B.C., K.C.V., A.C.D.), Vanderbilt University, Nashville, TN.ORCID 0000-0001-6382-5657
Cristina M YouwakimDepartment of Medicine (C.M.Y., B.F.L., K.K.F., S.M.J.R., K.G., D.L.M., L.M.D., C.C., Y.E.C., M.F.L., P.B.F., K.C.V., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.
Brenda F LeakeDepartment of Medicine (C.M.Y., B.F.L., K.K.F., S.M.J.R., K.G., D.L.M., L.M.D., C.C., Y.E.C., M.F.L., P.B.F., K.C.V., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.
Kristin K FullerDepartment of Medicine (C.M.Y., B.F.L., K.K.F., S.M.J.R., K.G., D.L.M., L.M.D., C.C., Y.E.C., M.F.L., P.B.F., K.C.V., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.
S M Jamshedur RahmanDepartment of Medicine (C.M.Y., B.F.L., K.K.F., S.M.J.R., K.G., D.L.M., L.M.D., C.C., Y.E.C., M.F.L., P.B.F., K.C.V., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0009-0000-8866-3957
Matthew M DunganDepartment of Pathology, Microbiology, and Immunology (A.L.G., M.M.D., A.B.C., K.C.V., A.C.D.), Vanderbilt University, Nashville, TN.ORCID 0000-0002-2989-5982
Katherine GuDepartment of Medicine (C.M.Y., B.F.L., K.K.F., S.M.J.R., K.G., D.L.M., L.M.D., C.C., Y.E.C., M.F.L., P.B.F., K.C.V., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.
Jesse L BoninDepartment of Immunology and Microbiology, Albany Medical College, NY (J.L.B., K.C.M.).ORCID 0009-0003-5595-3749
Ashley B CavnarDepartment of Pathology, Microbiology, and Immunology (A.L.G., M.M.D., A.B.C., K.C.V., A.C.D.), Vanderbilt University, Nashville, TN.ORCID 0000-0001-5081-9274
Danielle L MichellDepartment of Medicine (C.M.Y., B.F.L., K.K.F., S.M.J.R., K.G., D.L.M., L.M.D., C.C., Y.E.C., M.F.L., P.B.F., K.C.V., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0002-2048-4191
Lindsay M DavisonDepartment of Medicine (C.M.Y., B.F.L., K.K.F., S.M.J.R., K.G., D.L.M., L.M.D., C.C., Y.E.C., M.F.L., P.B.F., K.C.V., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0001-8387-4958
Calliope CutchinsDepartment of Medicine (C.M.Y., B.F.L., K.K.F., S.M.J.R., K.G., D.L.M., L.M.D., C.C., Y.E.C., M.F.L., P.B.F., K.C.V., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0009-0001-4293-4544
Yunli E ChuDepartment of Medicine (C.M.Y., B.F.L., K.K.F., S.M.J.R., K.G., D.L.M., L.M.D., C.C., Y.E.C., M.F.L., P.B.F., K.C.V., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0001-6120-1496
Shuai YuanDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, PA (S.Y.).ORCID 0000-0002-9590-6555
Arif YurdagulDepartment of Molecular and Cellular Physiology (A.Y.), LSU Health Sciences Center-Shreveport, LA.ORCID 0000-0002-7613-6313
James G TraylorDepartment of Pathology and Translational Pathobiology (J.G.T., A.W.O.), LSU Health Sciences Center-Shreveport, LA.ORCID 0000-0002-7119-6333
A Wayne OrrDepartment of Pathology and Translational Pathobiology (J.G.T., A.W.O.), LSU Health Sciences Center-Shreveport, LA.ORCID 0000-0002-2377-213X
Zachary A KohutekDepartment of Radiation Oncology (Z.A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0002-2472-9977
MacRae F LintonDepartment of Medicine (C.M.Y., B.F.L., K.K.F., S.M.J.R., K.G., D.L.M., L.M.D., C.C., Y.E.C., M.F.L., P.B.F., K.C.V., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0002-9277-0453
Katherine C MacNamaraDepartment of Immunology and Microbiology, Albany Medical College, NY (J.L.B., K.C.M.).ORCID 0000-0001-6202-4700
P Brent FerrellVanderbilt Institute for Infection, Immunology, and Inflammation (P.B.F., A.C.D.), Vanderbilt University, Nashville, TN.ORCID 0000-0003-1140-9154
Kasey C VickersDepartment of Pathology, Microbiology, and Immunology (A.L.G., M.M.D., A.B.C., K.C.V., A.C.D.), Vanderbilt University, Nashville, TN.ORCID 0000-0001-5643-3102
Meena S MadhurDepartment of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis (M.S.M.).ORCID 0000-0002-0407-634X
Jonathan D BrownDepartment of Molecular Physiology and Biophysics (K.C.V., J.D.B., A.C.D.), Vanderbilt University, Nashville, TN.ORCID 0000-0002-0359-6167
Amanda C DoranDepartment of Pathology, Microbiology, and Immunology (A.L.G., M.M.D., A.B.C., K.C.V., A.C.D.), Vanderbilt University, Nashville, TN.ORCID 0000-0002-1576-6274

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ben Ho Park · 1995 to 2026
$172.8M
Non-coding RNA & Bioinformatics CoreP01HL116263 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DAVIES, SEAN STEPHEN · 2014 to 2025
$24.7M
Stress Exacerbates Myocardial Ischemic Injury by Blocking Estrogen's Antidoxidant Protection in the Female HeartP20GM121307 · NIGMS · LOUISIANA STATE UNIV HSC SHREVEPORT · PI Vesna Tesic · 2018 to 2026
$23.6M
Nck Adaptor Proteins in Atherogenic Endothelial ActivationR01HL133497 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI ORR, ANTHONY WAYNE · 2016 to 2024
$3.8M
Critical Mediators of Inflammation Resolution and Immune Memory in AtherosclerosisR01HL159487 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DORAN, AMANDA C · 2021 to 2025
$3.2M
Matrix Signaling in Endothelial Cell DysfunctionR01HL098435 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI ORR, ANTHONY WAYNE · 2010 to 2020
$3.2M
Inflammation-resolution impairments in aging and atherosclerosisR01HL170249 · NHLBI · ALBANY MEDICAL COLLEGE · PI Gabrielle Fredman, Katherine C MacNamara · 2023 to 2026
$3.2M
In Situ Albumin Binding siRNAs for Triple Negative Breast Cancer Tumor Penetration and Molecularly Targeted TherapyR01CA260958 · NCI · VANDERBILT UNIVERSITY · PI COOK, REBECCA SARA, DUVALL, CRAIG LEWIS · 2021 to 2025
$3.0M
Elucidating the chromatin-dependent mechanisms governing chronic inflammatory activation of endothelial cells in atherosclerosis.R01HL146654 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BROWN, JONATHAN DAVID · 2020 to 2023
$2.4M
Dysregulations in Polyamine Metabolism During AtherosclerosisR01HL167758 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI Arif Yurdagul · 2023 to 2026
$2.2M
EphA2 regulation of atherosclerotic smooth muscle phenotypeR01HL173972 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI Anthony Wayne Orr · 2024 to 2026
$2.1M
EphA2 signaling in atherosclerotic fibroproliferative remodelingR01HL141155 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI ORR, ANTHONY WAYNE · 2019 to 2022
$1.8M
American Heart Association-American Stroke Association 17FTF33660643American Heart Association-American Stroke Association 971070NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA260958NHLBI NIH HHS F31 HL172670NHLBI NIH HHS P01 HL116263NHLBI NIH HHS R00 HL145131NHLBI NIH HHS R01 HL098435NHLBI NIH HHS R01 HL133497NHLBI NIH HHS R01 HL141155NHLBI NIH HHS R01 HL146654NHLBI NIH HHS R01 HL159487NHLBI NIH HHS R01 HL167758NHLBI NIH HHS R01 HL170249NHLBI NIH HHS R01 HL173598NHLBI NIH HHS R01 HL173972NIAID NIH HHS T32 AI138932NIGMS NIH HHS P20 GM121307
6 · The paper itself

Abstract

backgroundChronic inflammation is a major driver of atherosclerotic cardiovascular disease, and therapeutics that target inflammation reduce cardiac events beyond levels seen with strategies targeting cholesterol alone. RNA sequencing revealed increased expression of CaMK4 (calcium/calmodulin-dependent protein kinase IV) in advanced/unstable human carotid artery plaque. We validated this finding in mouse and human atherosclerotic lesions, demonstrating increased CaMK4 in plaque macrophages. Therefore, we hypothesized that CaMK4 would promote inflammation and impair resolution in atherosclerosis.

methodsWe obtained mice in which exon 3 within the kinase domain of CaMK4 is deleted, leading to degradation and deletion of the gene (

resultsHypercholesterolemic

conclusionsThese findings suggest that CaMK4 is an important regulator of the myelopoietic response to hypercholesterolemia through ATF6-mediated transcriptional regulation and that loss of functional CaMK4 promotes a proreparative phenotype in myeloid cells. Therefore, targeting CaMK4 may offer a unique way to target the progression of atherosclerosis.

Indexed as

Aortic DiseasesAtherosclerosisCalcium-Calmodulin-Dependent Protein Kinase Type 4MyelopoiesisAnimalsDisease Models, AnimalHumansHypercholesterolemiaMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNuclear Receptor Subfamily 4, Group A, Member 1Plaque, AtheroscleroticSignal TransductionCalcium-Calmodulin-Dependent Protein Kinase Type 4CAMK4 protein, humanCamk4 protein, mouseNr4a1 protein, mouseNuclear Receptor Subfamily 4, Group A, Member 1atherosclerosisbone marrowmacrophagesmonocytesmyelopoiesis

Identifiers

PMID40336480
PMCPMC12197841

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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.