Evidence map›Paper›PMID 27018592›Full record

ArticleThe Journal of clinical investigation2016

4-Dimensional light-sheet microscopy to elucidate shear stress modulation of cardiac trabeculation.

Juhyun Lee, Peng Fei, René R Sevag Packard, Hanul Kang, Hao Xu, Kyung In Baek, Nelson Jen, Junjie Chen, Hilary Yen, C-C Jay Kuo and 4 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
9.1field-weighted citation impact, top 2% 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

72 citing papers in PubMed, 124 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Emerging Light-Sheet Fluorescence Microscopy for Cardiac Vascular Imaging in Zebrafish.Current treatment options in cardiovascular medicine · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Light-Sheet Imaging to Reveal Cardiac Structure in Rodent Hearts.Journal of visualized experiments : JoVE · 2024
    Article
  13. Article
  14. Article
  15. 4D Light-sheet Imaging of Zebrafish Cardiac Contraction.Journal of visualized experiments : JoVE · 2024
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Imaging Approaches and the Quantitative Analysis of Heart Development.Journal of cardiovascular development and disease · 2023
    Review

12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Juhyun Lee
Peng Fei
René R Sevag Packard
Hanul Kang
Hao Xu
Kyung In Baek
Nelson Jen
Junjie Chen
Hilary Yen
C-C Jay Kuo
Neil C Chi
Chih-Ming Ho
Rongsong Li
Tzung K Hsiai
La Jolla Bioengineering Institute · USUniversity of Southern California · USVA Greater Los Angeles Healthcare System · USHuazhong University of Science and Technology · CN

Funding

CARDIOVASCULAR SCIENTIST TRAINING PROGRAMT32HL007895 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SHIVKUMAR, KALYANAM, WATSON, KAROL E · 1998 to 2023
$9.2M
Linking Spatial Variations Shear Stress-Oxidative StressR01HL083015 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HSIAI, TZUNG K · 2006 to 2015
$3.9M
Shear Stress and Light-Sheets to Study Cardiac TrabeculationR01HL129727 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HSIAI, TZUNG K, MARSDEN, ALISON L · 2015 to 2024
$3.5M
Electronica Impedance to Access Metabolically Active PlaqueR01HL118650 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HSIAI, TZUNG K · 2014 to 2022
$3.3M
Micro-Sensors to Study Electrical and Mechanical Coupling of Injured MyocardiumR01HL111437 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HSIAI, TZUNG K, XU, XIAOLEI · 2012 to 2020
$3.1M
Electrical Biophysical Forces Impact Cardiac MorphogenesisR01HD069305 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C · 2011 to 2015
$1.6M
NHLBI NIH HHS R01 HL083015NHLBI NIH HHS R01 HL111437NHLBI NIH HHS R01 HL118650NHLBI NIH HHS R01 HL129727NHLBI NIH HHS T32 HL007895NICHD NIH HHS R01 HD069305
6 · The paper itself

Abstract

Hemodynamic shear forces are intimately linked with cardiac development, during which trabeculae form a network of branching outgrowths from the myocardium. Mutations that alter Notch signaling also result in trabeculation defects. Here, we assessed whether shear stress modulates trabeculation to influence contractile function. Specifically, we acquired 4D (3D + time) images with light sheets by selective plane illumination microscopy (SPIM) for rapid scanning and deep axial penetration during zebrafish morphogenesis. Reduction of blood viscosity via gata1a morpholino oligonucleotides (MO) reduced shear stress, resulting in downregulation of Notch signaling and attenuation of trabeculation. Arrest of cardiomyocyte contraction either by troponin T type 2a (tnnt2a) MO or in weak atriumm58 (wea) mutants resulted in reduced shear stress and downregulation of Notch signaling and trabeculation. Integrating 4D SPIM imaging with synchronization algorithm demonstrated that coinjection of neuregulin1 mRNA with gata1 MO rescued trabeculation to restore contractile function in association with upregulation of Notch-related genes. Crossbreeding of Tg(flk:mCherry) fish, which allows visualization of the vascular system with the Tg(tp1:gfp) Notch reporter line, revealed that shear stress-mediated Notch activation localizes to the endocardium. Deleting endocardium via the clochesk4 mutants downregulated Notch signaling, resulting in nontrabeculated ventricle. Subjecting endothelial cells to pulsatile flow in the presence of the ADAM10 inhibitor corroborated shear stress-activated Notch signaling to modulate trabeculation.

Indexed as

Shear StrengthAnimalsAnimals, Genetically ModifiedHeart AtriaMicroscopy, FluorescenceMyocardial ContractionMyocardiumNeuregulin-1OrganogenesisReceptors, NotchSignal TransductionTroponin TZebrafishZebrafish ProteinsNeuregulin-1Receptors, Notchtnnt2a protein, zebrafishTroponin TZebrafish Proteins

Identifiers

PMID27018592
PMCPMC4855946
OpenAlexW2326707709

What OpenQuestion holds

Textmetadata
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.