Evidence map›Paper›PMID 22723297›Full record

ArticleCirculation research2012

Stimulated emission depletion live-cell super-resolution imaging shows proliferative remodeling of T-tubule membrane structures after myocardial infarction.

Eva Wagner, Marcel A Lauterbach, Tobias Kohl, Volker Westphal, George S B Williams, Julia H Steinbrecher, Jan-Hendrik Streich, Brigitte Korff, Hoang-Trong M Tuan, Brian Hagen and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed
13.1field-weighted citation impact, top 1% 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

120 citing papers in PubMed, 195 citations in OpenAlex.

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  11. Matriglycan maintains t-tubule structural integrity in cardiac muscle.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  20. Serial block face scanning electron microscopy reveals region-dependent remodelling of transverse tubules post-myocardial infarction.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022
    Article

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

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

17 authors at 4 institutions in 2 countries.

Eva WagnerHeart Research Center Goettingen, University Medicine Goettingen, Goettingen, Germany.
Marcel A Lauterbach
Tobias Kohl
Volker Westphal
George S B Williams
Julia H Steinbrecher
Jan-Hendrik Streich
Brigitte Korff
Hoang-Trong M Tuan
Brian Hagen
Stefan Luther
Gerd Hasenfuss
Ulrich Parlitz
M Saleet Jafri
Stefan W Hell
W Jonathan Lederer
Stephan E Lehnart
University of Maryland, Baltimore · USMax Planck Institute for Biophysical Chemistry · DECornell University · USMax Planck Institute for Dynamics and Self-Organization · DE

Funding

Calcium Entrained ArrhythmiasR01HL105239 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI JAFRI, MOHSIN SALEET, LEDERER, WILLIAM JONATHAN · 2011 to 2015
$4.9M
NHLBI NIH HHS 1R01 HL1105239-01NHLBI NIH HHS R01 HL105239
6 · The paper itself

Abstract

rationaleTransverse tubules (TTs) couple electric surface signals to remote intracellular Ca(2+) release units (CRUs). Diffraction-limited imaging studies have proposed loss of TT components as disease mechanism in heart failure (HF).

objectivesObjectives were to develop quantitative super-resolution strategies for live-cell imaging of TT membranes in intact cardiomyocytes and to show that TT structures are progressively remodeled during HF development, causing early CRU dysfunction. METHODS AND

resultsUsing stimulated emission depletion (STED) microscopy, we characterized individual TTs with nanometric resolution as direct readout of local membrane morphology 4 and 8 weeks after myocardial infarction (4pMI and 8pMI). Both individual and network TT properties were investigated by quantitative image analysis. The mean area of TT cross sections increased progressively from 4pMI to 8pMI. Unexpectedly, intact TT networks showed differential changes. Longitudinal and oblique TTs were significantly increased at 4pMI, whereas transversal components appeared decreased. Expression of TT-associated proteins junctophilin-2 and caveolin-3 was significantly changed, correlating with network component remodeling. Computational modeling of spatial changes in HF through heterogeneous TT reorganization and RyR2 orphaning (5000 of 20 000 CRUs) uncovered a local mechanism of delayed subcellular Ca(2+) release and action potential prolongation.

conclusionsThis study introduces STED nanoscopy for live mapping of TT membrane structures. During early HF development, the local TT morphology and associated proteins were significantly altered, leading to differential network remodeling and Ca(2+) release dyssynchrony. Our data suggest that TT remodeling during HF development involves proliferative membrane changes, early excitation-contraction uncoupling, and network fracturing.

Indexed as

NanotechnologyVentricular RemodelingAction PotentialsAnimalsCaveolin 3Computer SimulationDisease Models, AnimalExcitation Contraction CouplingFemaleFluorescent DyesImage Processing, Computer-AssistedIntracellular MembranesMembrane ProteinsMiceMice, Inbred C57BLMicroscopy, ConfocalCaveolin 3Fluorescent DyesjunctophilinMembrane ProteinsRyanodine Receptor Calcium Release Channel

Identifiers

PMID22723297
PMCPMC4219578
OpenAlexW2102311103

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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.