Evidence map›Paper›PMID 25368203›Full record

ArticleEuropean heart journal2015

Pravastatin reverses obesity-induced dysfunction of induced pluripotent stem cell-derived endothelial cells via a nitric oxide-dependent mechanism.

Mingxia Gu, Nicholas M Mordwinkin, Nigel G Kooreman, Jaecheol Lee, Haodi Wu, Shijun Hu, Jared M Churko, Sebastian Diecke, Paul W Burridge, Chunjiang He and 4 more

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

Article in European heart journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

26 citing papers in PubMed, 46 citations in OpenAlex.

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  12. Generation of Endothelial Cells From Human Pluripotent Stem Cells.Arteriosclerosis, thrombosis, and vascular biology · 2019
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Mingxia GuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Nicholas M MordwinkinStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Nigel G KooremanStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Jaecheol LeeStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Haodi WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Shijun HuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Jared M ChurkoStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Sebastian DieckeStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Paul W BurridgeStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Chunjiang HeStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Frances E BarronStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Sang-Ging OngStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Joseph D GoldStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Joseph C WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA joewu@stanford.edu.
Stanford University · US

Funding

Project 3: Effect of Age and Longevity Genes on Epigenomic MechanismsP01GM099130 · NIGMS · STANFORD UNIVERSITY · PI WEISSMAN, SHERMAN MORTON · 2011 to 2015
$11.4M
Pulmonary Hypertension Breakthrough InitiativeR24HL123767 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ALDRED, MICHEALA A, ERZURUM, SERPIL C. · 2014 to 2017
$10.1M
iPSC Derived EC as Surrogates Using Pulmonary Hypertension as a Prototype DiseaseU01HL107393 · NHLBI · STANFORD UNIVERSITY · PI RABINOVITCH, MARLENE, SNYDER, MICHAEL P. · 2011 to 2015
$8.7M
Induced pluripotent stem cells in the understanding and treatment of heart diseaseU01HL099776 · NHLBI · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, WU, JOSEPH C. · 2009 to 2015
$8.2M
Human Induced Pluripotent Stem Cells for Cardiovascular Disease ModelingR01HL113006 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2012 to 2025
$6.8M
Multi-Disciplinary Training Program in Cardiovascular Imaging at StanfordT32EB009035 · NIBIB · STANFORD UNIVERSITY · PI Koen Nieman, John M. Pauly · 2008 to 2026
$4.3M
Airway redox biochemistry as a deteriminant of asthma phenotype during adolescen*U10HL109250 · NHLBI · UNIVERSITY OF VIRGINIA · PI ERZURUM, SERPIL C., GASTON, BENJAMIN · 2011 to 2016
$4.2M
NHLBI NIH HHS HL107393NHLBI NIH HHS R01HL113006NHLBI NIH HHS R24 HL123767NHLBI NIH HHS U01 HL099776NHLBI NIH HHS U01 HL107393NHLBI NIH HHS U10 HL109250NIBIB NIH HHS T32 EB009035NIBIB NIH HHS T32EB009035NIGMS NIH HHS P01 GM099130
6 · The paper itself

Abstract

aimsHigh-fat diet-induced obesity (DIO) is a major contributor to type II diabetes and micro- and macro-vascular complications leading to peripheral vascular disease (PVD). Metabolic abnormalities of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from obese individuals could potentially limit their therapeutic efficacy for PVD. The aim of this study was to compare the function of iPSC-ECs from normal and DIO mice using comprehensive in vitro and in vivo assays. METHODS AND

resultsSix-week-old C57Bl/6 mice were fed with a normal or high-fat diet. At 24 weeks, iPSCs were generated from tail tip fibroblasts and differentiated into iPSC-ECs using a directed monolayer approach. In vitro functional analysis revealed that iPSC-ECs from DIO mice had significantly decreased capacity to form capillary-like networks, diminished migration, and lower proliferation. Microarray and ELISA confirmed elevated apoptotic, inflammatory, and oxidative stress pathways in DIO iPSC-ECs. Following hindlimb ischaemia, mice receiving intramuscular injections of DIO iPSC-ECs had significantly decreased reperfusion compared with mice injected with control healthy iPSC-ECs. Hindlimb sections revealed increased muscle atrophy and presence of inflammatory cells in mice receiving DIO iPSC-ECs. When pravastatin was co-administered to mice receiving DIO iPSC-ECs, a significant increase in reperfusion was observed; however, this beneficial effect was blunted by co-administration of the nitric oxide synthase inhibitor, N(ω)-nitro-l-arginine methyl ester.

conclusionThis is the first study to provide evidence that iPSC-ECs from DIO mice exhibit signs of endothelial dysfunction and have suboptimal efficacy following transplantation in a hindlimb ischaemia model. These findings may have important implications for future treatment of PVD using iPSC-ECs in the obese population.

Indexed as

Analysis of VarianceAnimalsApoptosisCell DifferentiationDiet, High-FatEndothelial CellsEnzyme InhibitorsFibroblastsHindlimbHydroxymethylglutaryl-CoA Reductase InhibitorsInduced Pluripotent Stem CellsInjections, IntramuscularIschemiaMice, Inbred C57BLMuscle, SkeletalMuscular DiseasesEnzyme InhibitorsHydroxymethylglutaryl-CoA Reductase InhibitorsNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide Synthase Type IIIPravastatinProto-Oncogene Proteins c-aktDiet-induced obesityEndothelial cellsHindlimb ischaemiaInduced pluripotent stem cellsPeripheral vascular diseaseStatins

Identifiers

PMID25368203
PMCPMC4381134
OpenAlexW1976967218

What OpenQuestion holds

Texttitle and abstract
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.