Evidence map›Paper›PMID 23991206›Full record

Trial reportPloS one2013

LDL cholesterol modulates human CD34+ HSPCs through effects on proliferation and the IL-17 G-CSF axis.

Thomas R Cimato, Beth A Palka, Jennifer K Lang, Rebeccah F Young

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

27 citing papers in PubMed, 45 citations in OpenAlex.

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  14. Fine-Tuning of Cholesterol Homeostasis Controls Erythroid Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
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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

4 authors at 1 institution in 1 country.

Thomas R CimatoDepartment of Medicine/Division of Cardiovascular Medicine, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Clinical and Translational Research Center, Buffalo, New York, USA. tcimato@buffalo.edu
Beth A Palka
Jennifer K Lang
Rebeccah F Young
University at Buffalo, State University of New York · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHypercholesterolemia plays a critical role in atherosclerosis. CD34+ CD45dim Lineage- hematopoietic stem/progenitor cells (HSPCs) give rise to the inflammatory cells linked to atherosclerosis. In mice, high cholesterol levels mobilize HSPCs into the bloodstream, and promote their differentiation to granulocytes and monocytes. The objective of our study was to determine how cholesterol levels affect HSPC quantity in humans.

methodsWe performed a blinded, randomized hypothesis generating study in human subjects (n=12) treated sequentially with statins of differing potencies to vary lipid levels. CD34+ HSPC levels in blood were measured by flow cytometry. Hematopoietic colony forming assays confirmed the CD34+ population studied as HSPCs with multlineage differentiation potential. Mobilizing cytokine levels were measured by ELISA.

resultsThe quantity of HSPCs was 0.15 ± 0.1% of buffy coat leukocytes. We found a weak, positive correlation between CD34+ HSPCs and both total and LDL cholesterol levels (r(2)=0.096, p < 0.025). Additionally, we tested whether cholesterol modulates CD34+ HSPCs through direct effects or on the levels of mobilizing cytokines. LDL cholesterol increased cell surface expression of CXCR4, G-CSFR affecting HSPC migration, and CD47 mediating protection from phagocytosis by immune cells. LDL cholesterol also increased proliferation of CD34+ HSPCs (28 ± 5.7%, n=6, p < 0.03). Finally, the HSPC mobilizing cytokine G-CSF (r(2)=0.0683, p < 0.05), and its upstream regulator IL-17 (r(2)=0.0891, p < 0.05) both correlated positively with LDL cholesterol, while SDF-1 levels were not significantly affected.

conclusionsOur findings support a model where LDL cholesterol levels positively correlate with CD34+ HSPC levels in humans through effects on the levels of G-CSF via IL-17 promoting mobilization of HSPCs, and by direct effects of LDL cholesterol on HSPC proliferation. The findings are provocative of further study to determine if HSPCs, like cholesterol levels, are linked to CVD events.

Indexed as

Cell ProliferationAdultAntigens, CD34Cholesterol, LDLFemaleFlow CytometryGranulocyte Colony-Stimulating FactorHematopoietic Stem CellsHumansInterleukin-17MaleMiddle AgedAntigens, CD34Cholesterol, LDLGranulocyte Colony-Stimulating FactorInterleukin-17

Identifiers

PMID23991206
PMCPMC3753239
OpenAlexW1985315670

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.