Evidence map›Paper›PMID 21953346›Full record

ArticleAnnals of the rheumatic diseases2012

Mycophenolate mofetil but not atorvastatin attenuates atherosclerosis in lupus-prone LDLr(-/-) mice.

Sander I van Leuven, Yanice V Mendez-Fernandez, Ashley J Wilhelm, Nekeithia S Wade, Curtis L Gabriel, John J Kastelein, Erik S Stroes, Paul P Tak, Amy S Major

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

Article in Annals of the rheumatic diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 2 pooled it
2.5field-weighted citation impact, top 11% 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

41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 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

9 authors at 2 institutions in 2 countries.

Sander I van LeuvenDepartment of Medicine/Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. s.i.vanleuven@amc.uva.nl
Yanice V Mendez-Fernandez
Ashley J Wilhelm
Nekeithia S Wade
Curtis L Gabriel
John J Kastelein
Erik S Stroes
Paul P Tak
Amy S Major
Vanderbilt University · USAcademic Medical Center · NL

Funding

Role of iNKT Cells in Autoimmunity and AtherosclerosisR01HL089310 · NHLBI · VANDERBILT UNIVERSITY · PI MAJOR, AMY S · 2007 to 2011
$2.2M
Accelerated Atherosclerosis and system lupus erythematosusR01HL088364 · NHLBI · VANDERBILT UNIVERSITY · PI MAJOR, AMY S · 2008 to 2011
$1.6M
NHLBI NIH HHS R01 HL088364NHLBI NIH HHS R01HL088364NHLBI NIH HHS R01 HL089310NHLBI NIH HHS R01HL089310
6 · The paper itself

Abstract

rationaleRecent clinical and preclinical studies have demonstrated that systemic lupus erythematosus (SLE) is associated with an increased risk for cardiovascular disease (CVD). However, unlike in the general population, little is known regarding the efficacy of atheroprotective interventions in patients with SLE. The current study aims to determine the benefit of lymphocyte inhibition on reducing the atherosclerotic burden in SLE-susceptible LDLr-deficient mice.

methodsFemale LDLr(-/-) mice were lethally irradiated and reconstituted with bone marrow from C57Bl/6 mice (LDLr.B6) or the SLE-susceptible B6.Sle1.2.3 mice (LDLr.Sle). At 16 weeks post transplant, mice were treated with atorvastatin (10 mg/kg), mycophenolate mofetil (MMF; 40 mg/kg), or both (MMF-A) for 8 weeks, after which the extent of atherosclerosis and the presence of SLE were assessed.

resultsFollowing 8 weeks of treatment, we observed that atorvastatin-mediated reduction in cholesterol levels attenuated atherogenesis in LDLr.B6 mice but failed to significantly reduce atherosclerotic lesion size in LDLr.Sle mice, in spite of a significant reduction in serum cholesterol levels. Treatment with MMF and MMF-A attenuated atherogenesis in LDLr.B6 and LDLr.Sle mice. In addition, MMF-containing regimens inhibited recruitment of CD4+ T cells to atherosclerotic lesions in LDLr.Sle mice. In these mice, MMF also reduced the proportion of activated splenic T cells, as well as interleukin 10 secretion by T cells. With regard to lupus activity, MMF had no overt effect on anti-double-stranded DNA (dsDNA) antibody titres or kidney function and pathology.

conclusionsThe current study demonstrates that reduction of cholesterol levels alone is not atheroprotective in lupus-mediated atherogenesis. This is the first study to demonstrate that MMF reduces the atherosclerotic burden in a model of lupus-accelerated atherosclerosis. Our results suggest that MMF treatment may prove beneficial in preventing CVD in patients with SLE.

Indexed as

AnimalsAtherosclerosisAtorvastatinCD4-Positive T-LymphocytesCholesterolDisease Models, AnimalDrug Evaluation, PreclinicalDrug Therapy, CombinationFemaleGenetic Predisposition to DiseaseHeptanoic AcidsHydroxymethylglutaryl-CoA Reductase InhibitorsImmunity, CellularImmunosuppressive AgentsLupus Erythematosus, SystemicMiceAtorvastatinCholesterolHeptanoic AcidsHydroxymethylglutaryl-CoA Reductase InhibitorsImmunosuppressive AgentsMycophenolic AcidPyrroles

Identifiers

PMID21953346
PMCPMC3306213
OpenAlexW2066486914

What OpenQuestion 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 OpenQuestion graph.