Evidence map›Paper›PMID 27091183›Full record

ArticleJournal of the American Heart Association2016

Integrated Regional Cardiac Hemodynamic Imaging and RNA Sequencing Reveal Corresponding Heterogeneity of Ventricular Wall Shear Stress and Endocardial Transcriptome.

Margaret E McCormick, Elisabetta Manduchi, Walter R T Witschey, Robert C Gorman, Joseph H Gorman, Yi-Zhou Jiang, Christian J Stoeckert, Alex J Barker, Michael Markl, Peter F Davies

Open access · goldAbstract read
In one paragraph

Article in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 17% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Shear stress-induced CaBiological research · 2026
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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

10 authors at 2 institutions in 1 country.

Margaret E McCormickInstitute for Medicine and Engineering, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Elisabetta ManduchiInstitute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Walter R T WitscheyDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Robert C GormanDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Joseph H GormanDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Yi-Zhou JiangInstitute for Medicine and Engineering, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Christian J StoeckertInstitute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Alex J BarkerDepartment of Radiology, Northwestern University, Chicago, IL.
Michael MarklDepartment of Radiology, Northwestern University, Chicago, IL Department of Biomedical Engineering, Northwestern University, Chicago, IL.
Peter F DaviesInstitute for Medicine and Engineering, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA pfd@mail.med.upenn.edu.
University of Pennsylvania · USNorthwestern University · US

Funding

Multidisciplinary Training in Cardiovascular BiologyT32HL007954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2000 to 2019
$9.9M
Quantitative Methods for Optimizing IMR RepairR01HL073021 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI GORMAN, ROBERT C, SACKS, MICHAEL S · 2004 to 2022
$7.6M
Functional Cardiovascular 4D MRI in Congenital Heart DiseaseR01HL115828 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MARKL, MICHAEL, RIGSBY, CYNTHIA K · 2012 to 2021
$5.2M
Hemodynamic Loading of the Left Ventricle and Aorta in Aortic Valve DiseaseK25HL119608 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI BARKER, ALEXANDER J. · 2014 to 2018
$819k
Nuclear Magnetic Tirho Relaxation in Acute and Chronic Myocardial InfarctionsR00HL108157 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI WITSCHEY, WALTER R.T. · 2014 to 2016
$747k
Epigenetic regulation of endothelial phenotype by flow and hypercholesterolemia in vivo and in vitroK99HL127272 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI JIANG, YIZHOU · 2016 to 2017
$216k
NHLBI NIH HHS K25 HL119608NHLBI NIH HHS K99 HL127272NHLBI NIH HHS P01 HL06220NHLBI NIH HHS R00 HL108157NHLBI NIH HHS R01 HL073021NHLBI NIH HHS R01 HL115828NHLBI NIH HHS T32 HL007954NHLBI NIH HHS T32 HL07954
6 · The paper itself

Abstract

backgroundUnlike arteries, in which regionally distinct hemodynamics are associated with phenotypic heterogeneity, the relationships between endocardial endothelial cell phenotype and intraventricular flow remain largely unexplored. We investigated regional differences in left ventricular wall shear stress and their association with endocardial endothelial cell gene expression. METHODS AND

resultsLocal wall shear stress was calculated from 4-dimensional flow magnetic resonance imaging in 3 distinct regions of human (n=8) and pig (n=5) left ventricle: base, adjacent to the outflow tract; midventricle; and apex. In both species, wall shear stress values were significantly lower in the apex and midventricle relative to the base; oscillatory shear index was elevated in the apex. RNA sequencing of the endocardial endothelial cell transcriptome in pig left ventricle (n=8) at a false discovery rate ≤10% identified 1051 genes differentially expressed between the base and the apex and 327 between the base and the midventricle; no differentially expressed genes were detected at this false discovery rate between the apex and the midventricle. Enrichment analyses identified apical upregulation of genes associated with translation initiation including mammalian target of rapamycin, and eukaryotic initiation factor 2 signaling. Genes of mitochondrial dysfunction and oxidative phosphorylation were also consistently upregulated in the left ventricular apex, as were tissue factor pathway inhibitor (mean 50-fold) and prostacyclin synthase (5-fold)-genes prominently associated with antithrombotic protection.

conclusionsWe report the first spatiotemporal measurements of wall shear stress within the left ventricle and linked regional hemodynamics to heterogeneity in ventricular endothelial gene expression, most notably to translation initiation and anticoagulation properties in the left ventricular apex, in which oscillatory shear index is increased and wall shear stress is decreased.

Indexed as

AnimalsCardiac Imaging TechniquesEndocardiumFemaleGene Expression ProfilingGenomic LibraryHeart VentriclesHemodynamicsHumansMagnetic Resonance ImagingMaleRNAShear StrengthSwineVentricular Function, LeftYoung AdultRNA4‐dimensional flow magnetic resonance imagingendocardiumgene expressionhemodynamicsventricle

Identifiers

PMID27091183
PMCPMC4859290
OpenAlexW2336878672

What OpenQuestion holds

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LicenceCC BY-NC
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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.