Evidence map›Paper›PMID 32646751›Full record

ArticleEBioMedicine2020

Hyperlipidaemia and IFNgamma/TNFalpha Synergism are associated with cholesterol crystal formation in Endothelial cells partly through modulation of Lysosomal pH and Cholesterol homeostasis.

Yvonne Baumer, Amit K Dey, Cristhian A Gutierrez-Huerta, Noor O Khalil, Yusuke Sekine, Gregory E Sanda, Jie Zhuang, Ankit Saxena, Erin Stempinski, Youssef A Elnabawi and 17 more

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

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

13 citing papers in PubMed, 24 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

27 authors at 7 institutions in 1 country.

Yvonne BaumerSection of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Amit K DeySection of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Cristhian A Gutierrez-HuertaSocial Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Noor O KhalilSection of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Yusuke SekineCenter for Molecular Medicine, National Heart Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Gregory E SandaSection of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Jie ZhuangCardiovascular and Cancer Genetics Laboratory, National Heart Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Ankit SaxenaFlow Cytometry Core, National Heart Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Erin StempinskiElectron Microscopy Core Facility, National Heart, Lung, and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Youssef A ElnabawiSection of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Pradeep K DagurFlow Cytometry Core, National Heart Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Qimin NgSection of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Heather L TeagueSection of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Andrew KeelSection of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Justin A RodanteSection of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
William A BoisvertCenter for Cardiovascular Research, John A Burns School of Medicine, University of Hawaii, 651 Ilalo Street, Honolulu, HI 96813, USA.
Lam C TsoiDepartment of Dermatology, University of Michigan, 1301 E. Catherine Street, Ann Arbor, MI 48109, USA.
Johann E GudjonssonDepartment of Dermatology, University of Michigan, 1301 E. Catherine Street, Ann Arbor, MI 48109, USA.
Christopher K E BleckElectron Microscopy Core Facility, National Heart, Lung, and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Marcus Y ChenSection of Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
David A BluemkeDepartment of Radiology, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA.
Joel M GelfandDepartment of Dermatology, Hospital of the University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.
Daniella M SchwartzGenetics and Pathogenesis of Allergy Section, National Institute of Allergy and Infectious Diseases, 10 Center Drive, Bethesda, MD 20892, USA.
Howard S KruthSection of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Tiffany M Powell-WileySocial Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Martin P PlayfordSection of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA.
Nehal N MehtaSection of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA. Electronic address: nehal.mehta@nih.gov.
National Heart Lung and Blood Institute · USUniversity of Michigan–Ann Arbor · USCancer Genetics (United States) · USHospital of the University of Pennsylvania · USNational Institute of Allergy and Infectious Diseases · USUniversity of Hawaiʻi at Mānoa · USUniversity of Wisconsin–Madison · US

Funding

The Role of gp120 on Cardiovascular Disease in People Living with HIVU54MD007601 · NIMHD · UNIVERSITY OF HAWAII AT MANOA · PI Jerris Robert Hedges · 2017 to 2026
$59.5M
Human Translational Studies of Inflammation and Cardiometabolic Diseases: The Psoriasis, Atherosclerosis and Cardiometabolic disease (PACI) InitiativeZIAHL006193 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI SACK, MICHAEL · 2014 to 2023
$25.0M
Cardiovascular CT Clinical ResearchZIAHL006220 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI CHEN, MARCUS · 2017 to 2025
$22.5M
Electron Microscopy CoreZICHL005906 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI SYED, ZULFEQHAR · 2009 to 2025
$12.9M
In-vitro and Pre-clinical Translational Studies of Inflammation and AtherosclerosisZIAHL006235 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI SACK, MICHAEL · 2018 to 2023
$6.7M
University of Michigan Skin Biology and Diseases Resource-based CenterP30AR075043 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Johann Eli Gudjonsson · 2019 to 2026
$6.6M
Pilot Study for Geospatial Analysis of Neighborhood Environmental Stress in Relation to Biological Markers of Cardiovascular Health and Health Behaviors in WomenZIAHL006252 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI POWELL-WILEY, TIFFANY · 2020 to 2025
$5.7M
NIAMS NIH HHS P30 AR075043NIMHD NIH HHS U54 MD007601
6 · The paper itself

Abstract

backgroundInflammation plays an important role in the development of cardiovascular disease (CVD). Patients with chronic inflammation diseases have high levels of inflammation and early fatal myocardial infarction due to early, unstable coronary plaques. Cholesterol crystals (CC) play a key role in atherogenesis. However, the underlying mechanisms of endothelial cell (EC)-derived CC formation are not well understood in chronic inflammation.

methodsWe utilized a combination of a mouse psoriasis model (K14-Rac1V12 mouse model) and human psoriasis patients to study the effect of inflammatory cytokines on CC formation in ECs. Lysosomal pH, alterations in lipid load and inflammatory proteins were evaluated as potential mechanisms linking inflammatory cytokines to CC formation. Coronary CT angiography was performed (n = 224) to characterize potential IFNγ and TNFα synergism on vascular diseases in vivo.

findingsWe detected CC presence in the aorta of K14-Rac1V12 mice on chow diet. IFNγ and TNFα were found to synergistically increase LDL-induced CC formation by almost 2-fold. There was an increase in lysosomal pH accompanied by a 28% loss in pH-dependent lysosomal signal and altered vATPaseV1E1 expression patterns. In parallel, we found that LDL+IFNγ/TNFα treatments increased free cholesterol content within EC and led to a decrease in SOAT-1 expression, an enzyme critically involved cholesterol homeostasis. Finally, the product of IFNγ and TNFα positively associated with early non-calcified coronary burden in patients with psoriasis (n = 224; β = 0.28, p < 0.001).

interpretationOur results provide evidence that IFNγ and TNFα accelerate CC formation in endothelial cells in part by altering lysosomal pH and free cholesterol load. These changes promote early atherogenesis and contribute to understanding the burden of CVD in psoriasis.

fundingFunding was provided by the Intramural Research Program at NIH (NNM) and the National Psoriasis Foundation (NNM and YB).

Indexed as

AdultAgedAnimalsCells, CulturedCholesterolCytokinesDisease Models, AnimalEndothelial CellsFemaleFlow CytometryHomeostasisHumansHydrogen-Ion ConcentrationHyperlipidemiasInflammation MediatorsInterferon-gammaCholesterolCytokinesInflammation MediatorsInterferon-gammaTumor Necrosis Factor-alphaAtherosclerosisCholesterol crystalsEndotheliumInflammationLipid metabolismLysosomal functionPsoriasis

Identifiers

PMID32646751
PMCPMC7502673
OpenAlexW3040563619

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LicenceCC BY
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Registered trials

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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.