Evidence map›Paper›PMID 37706321›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2023

Confounding Effects of Tamoxifen: Cautionary and Practical Considerations for the Use of Tamoxifen-Inducible Mouse Models in Atherosclerosis Research-Brief Report.

Allison M Dubner, Sizhao Lu, Austin J Jolly, Tysen Noble, Tyler Hinthorn, Raphael A Nemenoff, Karen S Moulton, Mark W Majesky, Mary C M Weiser-Evans

Open access · greenAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2023. 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
4.1field-weighted citation impact, top 6% 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, 13 citations in OpenAlex.

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  8. Expression and function of β-site amyloid precursor protein-cleaving enzyme 2 in vascular endothelium.American journal of physiology. Heart and circulatory physiology · 2025
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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

9 authors at 2 institutions in 1 country.

Allison M DubnerDepartment of Medicine, Division of Renal Diseases and Hypertension (A.M.D., S.L., A.J., T.N., T.H., R.A.N., M.C.M.W.-E.), University of Colorado Anschutz Medical Campus, Aurora.ORCID 0000-0001-8027-7410
Sizhao LuDepartment of Medicine, Division of Renal Diseases and Hypertension (A.M.D., S.L., A.J., T.N., T.H., R.A.N., M.C.M.W.-E.), University of Colorado Anschutz Medical Campus, Aurora.ORCID 0000-0002-9892-8784
Austin J JollyDepartment of Medicine, Division of Renal Diseases and Hypertension (A.M.D., S.L., A.J., T.N., T.H., R.A.N., M.C.M.W.-E.), University of Colorado Anschutz Medical Campus, Aurora.ORCID 0000-0001-6458-4648
Tysen NobleDepartment of Medicine, Division of Renal Diseases and Hypertension (A.M.D., S.L., A.J., T.N., T.H., R.A.N., M.C.M.W.-E.), University of Colorado Anschutz Medical Campus, Aurora.ORCID 0009-0000-8841-6470
Tyler HinthornDepartment of Medicine, Division of Renal Diseases and Hypertension (A.M.D., S.L., A.J., T.N., T.H., R.A.N., M.C.M.W.-E.), University of Colorado Anschutz Medical Campus, Aurora.
Raphael A NemenoffDepartment of Medicine, Division of Renal Diseases and Hypertension (A.M.D., S.L., A.J., T.N., T.H., R.A.N., M.C.M.W.-E.), University of Colorado Anschutz Medical Campus, Aurora.
Karen S MoultonDepartment of Medicine, Division of Cardiology (K.S.M.), University of Colorado Anschutz Medical Campus, Aurora.ORCID 0000-0001-9836-6614
Mark W MajeskyCenter for Developmental Biology & Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA (M.W.M.).ORCID 0000-0003-4267-6220
Mary C M Weiser-EvansDepartment of Medicine, Division of Renal Diseases and Hypertension (A.M.D., S.L., A.J., T.N., T.H., R.A.N., M.C.M.W.-E.), University of Colorado Anschutz Medical Campus, Aurora.ORCID 0000-0002-6239-2412
University of Colorado Anschutz Medical Campus · USCenter for Infectious Disease Research · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Reprogramming of mature smooth muscle cells to vascular progenitor cellsR01HL121877 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MARK W. MAJESKY, Mary CM Weiser-Evans · 2015 to 2026
$7.8M
NRSA Training CoreTL1TR002533 · NCATS · UNIVERSITY OF COLORADO DENVER · PI CICUTTO, LISA · 2018 to 2022
$3.0M
PTEN promoter hypermethylation underlies vascular disease progressionR01HL151331 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI WEISER-EVANS, MARY CM · 2021 to 2024
$2.3M
Role of Smooth Muscle-derived Vascular Progenitor Cells (AdvSca1-SM) in Vasa Vasorum Expansion and Atherosclerotic Plaque ProgressionF31HL160149 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI DUBNER, ALLISON M · 2021 to 2023
$86k
NCATS NIH HHS TL1 TR002533NCI NIH HHS P30 CA046934NHLBI NIH HHS F31 HL160149NHLBI NIH HHS R01 HL121877NHLBI NIH HHS R01 HL151331
6 · The paper itself

Abstract

backgroundIn recent years, fate-mapping lineage studies in mouse models have led to major advances in vascular biology by allowing investigators to track specific cell populations in vivo. One of the most frequently used lineage tracing approaches involves tamoxifen-inducible Cre

methodsTo elucidate off-target effects of tamoxifen, male and female mice were either unmanipulated or injected with tamoxifen or corn oil. All mice received PCSK9 (proprotein convertase subtilisin/kexin type 9)-AAV (adeno-associated virus) injections and a modified Western diet to induce hypercholesterolemia. After 2 weeks, serum cholesterol and liver morphology were assessed. To determine the duration of any tamoxifen effects in long-term atherosclerosis experiments, mice received either 12 days of tamoxifen at baseline or 12 days plus 2 sets of 5-day tamoxifen boosters; all mice received PCSK9-AAV injections and a modified Western diet to induce hypercholesterolemia. After 24 weeks, serum cholesterol and aortic sinus plaque burden were measured.

resultsAfter 2 weeks of atherogenic treatment, mice injected with tamoxifen demonstrated significantly reduced serum cholesterol levels compared with uninjected- or corn oil-treated mice. However, there were no differences in PCSK9-mediated knockdown of LDL (low-density lipoprotein) receptors between the groups. Additionally, tamoxifen-treated mice exhibited significantly increased hepatic lipid accumulation compared with the other groups. Finally, the effects of tamoxifen remained for at least 8 weeks after completion of injections, with mice demonstrating persistent decreased serum cholesterol and impaired atherosclerotic plaque formation.

conclusionsIn this study, we establish that tamoxifen administration results in decreased serum cholesterol, decreased plaque formation, and increased hepatic lipid accumulation. These alterations represent significant confounding variables in atherosclerosis research, and we urge future investigators to take these findings into consideration when planning and executing their own atherosclerosis experiments.

Indexed as

AtherosclerosisHypercholesterolemiaPlaque, AtheroscleroticAnimalsCholesterolCorn OilFemaleMaleMiceMice, Inbred C57BLProprotein Convertase 9Receptors, LDLCholesterolCorn OilPCSK9 protein, humanProprotein Convertase 9Receptors, LDLcorn oilhypercholesterolemialipoproteinsplaquetamoxifen

Identifiers

PMID37706321
PMCPMC10615862
OpenAlexW4386725600

What Socratic holds

Texttitle and abstract
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.