Evidence mapPaperPMID 31871049Full record

ArticleThe Journal of biological chemistry2020

ACE overexpression in myeloid cells increases oxidative metabolism and cellular ATP.

Duo-Yao Cao, Weston R Spivia, Luciana C Veiras, Zakir Khan, Zhenzi Peng, Anthony E Jones, Ellen A Bernstein, Suguru Saito, Derick Okwan-Duodu, Sarah J Parker and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

42 citing papers in PubMed, 40 citations in OpenAlex.

  1. Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026
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  14. Cancers · 2024
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  18. EGF-Receptor-Dependent TLR7 Signaling in Macrophages Promotes Glomerular Injury in Crescentic Glomerulonephritis.Laboratory investigation; a journal of technical methods and pathology · 2023
    Article
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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

14 authors at 2 institutions in 1 country.

Duo-Yao CaoDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Weston R SpiviaSmidt Heart Institute and Advanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048.ORCID 0000-0003-2764-7763
Luciana C VeirasDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Zakir KhanDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Zhenzi PengDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Anthony E JonesDepartment of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California 90095.
Ellen A BernsteinDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Suguru SaitoDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Derick Okwan-DuoduDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Sarah J ParkerSmidt Heart Institute and Advanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Jorge F GianiDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048.ORCID 0000-0003-0481-6595
Ajit S DivakaruniDepartment of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California 90095.
Jennifer E Van EykSmidt Heart Institute and Advanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Kenneth E BernsteinDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048 Kenneth.Bernstein@cshs.org.
Cedars-Sinai Medical Center · USUniversity of California, Los Angeles · US

Funding

Pilot & Feasibility ProgramP30DK063491 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2003 to 2025
$5.4M
TUMOR CELL SURFACES AND CHROMOSOMEST32CA009056 · UNIVERSITY OF CALIFORNIA LOS ANGELES · 1985 to 2025
$2.8M
TRAINING PROGRAM IN ENDOCRINOLOGY AND DIABETEST32DK007770 · CEDARS-SINAI MEDICAL CENTER · 1999 to 2003
$706k
NCI NIH HHS T32 CA009056NHLBI NIH HHS K99 HL141638NHLBI NIH HHS P01 HL129941NHLBI NIH HHS R00 HL128787NHLBI NIH HHS R01 HL111362NHLBI NIH HHS R01 HL132075NHLBI NIH HHS R01 HL142672NIAID NIH HHS R21 AI114965NIDDK NIH HHS P30 DK063491NIDDK NIH HHS T32 DK007770
6 · The paper itself

Abstract

Angiotensin-converting enzyme (ACE) affects blood pressure. In addition, ACE overexpression in myeloid cells increases their immune function. Using MS and chemical analysis, we identified marked changes of intermediate metabolites in ACE-overexpressing macrophages and neutrophils, with increased cellular ATP (1.7-3.0-fold) and Krebs cycle intermediates, including citrate, isocitrate, succinate, and malate (1.4-3.9-fold). Increased ATP is due to ACE C-domain catalytic activity; it is reversed by an ACE inhibitor but not by an angiotensin II AT1 receptor antagonist. In contrast, macrophages from ACE knockout (null) mice averaged only 28% of the ATP levels found in WT mice. ACE overexpression does not change cell or mitochondrial size or number. However, expression levels of the electron transport chain proteins NDUFB8 (complex I), ATP5A, and ATP5β (complex V) are significantly increased in macrophages and neutrophils, and COX1 and COX2 (complex IV) are increased in macrophages overexpressing ACE. Macrophages overexpressing ACE have increased mitochondrial membrane potential (24% higher), ATP production rates (29% higher), and maximal respiratory rates (37% higher) compared with WT cells. Increased cellular ATP underpins increased myeloid cell superoxide production and phagocytosis associated with increased ACE expression. Myeloid cells overexpressing ACE indicate the existence of a novel pathway in which myeloid cell function can be enhanced, with a key feature being increased cellular ATP.

Indexed as

Adenosine TriphosphateAngiotensin-Converting Enzyme InhibitorsAnimalsCitric Acid CycleCyclooxygenase 1Cyclooxygenase 2Electron Transport Complex IMacrophagesMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMitochondrial Proton-Translocating ATPasesMyeloid CellsNeutrophilsOxidation-ReductionAdenosine TriphosphateAngiotensin-Converting Enzyme InhibitorsATP5A1 protein, mouseCyclooxygenase 1Cyclooxygenase 2Electron Transport Complex IMembrane ProteinsMitochondrial Proton-Translocating ATPasesNDUFB8 protein, mousePeptidyl-Dipeptidase APtgs1 protein, mousePtgs2 protein, mouseangiotensin-converting enzyme (ACE)ATPelectron transport chainmacrophagemitochondrianeutrophiloxidative metabolism

Identifiers

PMID31871049
PMCPMC6996878
OpenAlexW2998350284

What Socratic holds

Textmetadata
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.