Evidence map›Paper›PMID 27255730›Full record

ArticleJournal of molecular and cellular cardiology2016

Cholesterol is required for maintaining T-tubule integrity and intercellular connections at intercalated discs in cardiomyocytes.

Yanqi Zhu, Caimei Zhang, Biyi Chen, Rong Chen, Ang Guo, Jiang Hong, Long-Sheng Song

Abstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Cardiotoxicity as a Possible Side Effect of Statins.Reviews in cardiovascular medicine · 2023
    Review
  4. Review of Recent Laboratory and Experimental Data on Cardiotoxicity of Statins.Journal of cardiovascular development and disease · 2022
    Review
  5. Article
  6. Review
  7. Article
  8. Atorvastatin, but not pravastatin, inhibits cardiac Akt/mTOR signaling and disturbs mitochondrial ultrastructure in cardiac myocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  9. Article
  10. Review
  11. Article
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

7 authors at 2 institutions in 2 countries.

Yanqi ZhuDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China; Division of Cardiovascular Medicine, Department of Internal Medicine, François M. Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Caimei ZhangDivision of Cardiovascular Medicine, Department of Internal Medicine, François M. Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Biyi ChenDivision of Cardiovascular Medicine, Department of Internal Medicine, François M. Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Rong ChenDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China; Department of Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China.
Ang GuoDivision of Cardiovascular Medicine, Department of Internal Medicine, François M. Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Jiang HongDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China; Department of Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China.
Long-Sheng SongDivision of Cardiovascular Medicine, Department of Internal Medicine, François M. Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Veterans Affairs Medical Center, Iowa City, IA 52242, USA. Electronic address: long-sheng-song@uiowa.edu.
University of Iowa · USShanghai First People's Hospital · CN

Funding

Novel Functions of the E-C Coupling Structural Protein Junctophilin-2 in the HeartR01HL130346 · NHLBI · UNIVERSITY OF IOWA · PI SONG, LONG-SHENG · 2016 to 2023
$4.4M
T-tubule remodeling and Ca2+-dependent arrhythmogenesis in cardiomyopathies.R01HL090905 · NHLBI · UNIVERSITY OF IOWA · PI SONG, LONG-SHENG · 2008 to 2017
$4.0M
BLRD VA I01 BX002334NHLBI NIH HHS R01 HL090905NHLBI NIH HHS R01 HL130346
6 · The paper itself

Abstract

backgroundsLow serum cholesterol levels are associated with cardiac arrhythmias and poor prognosis in patients with chronic heart failure. However, the underlying mechanisms by which decreases in cholesterol content lead to cardiac dysfunction remain unclear. Multiple studies have implicated damage to cardiac transverse (T)-tubules as a key mediator of excitation-contraction (E-C) coupling dysfunction and heart failure. Since the T-tubule membrane system is enriched in cholesterol, we hypothesized that depletion of membrane cholesterol promotes T-tubule remodeling and E-C coupling dysfunction. METHODS AND

resultsWe first examined the impact of membrane cholesterol depletion on T-tubule architecture by treating isolated C57BL/6 murine cardiomyocytes with methyl-β-cyclodextrin (MβCD). T-tubule structural integrity was progressively decreased by MβCD in a concentration- and time-dependent manner. Membrane cholesterol depletion also promoted a severe decrease in the amplitude of Ca(2+) transients and an increase in Ca(2+) release dyssynchrony as well as a significant increase in the frequency of spontaneous Ca(2+) sparks. Reintroduction of cholesterol restored T-tubule integrity and partially restored Ca(2+) handling properties in acutely-treated myocytes and slowed T-tubule deterioration in response to chronic MβCD exposure. Studies were extended to determine the impact of membrane cholesterol depletion on T-tubule structure in intact hearts. In addition to T-tubule remodeling, Langendorff perfusion of MβCD resulted in rapid and severe disruption of the intercellular connections between cardiomyocytes, in particular at intercalated disc regions in intact hearts.

conclusionsThese data provide the first evidence that cholesterol plays a critical role in maintaining cardiac T-tubule structure as well as the integrity of intercalated discs.

Indexed as

Excitation Contraction CouplingAnimalsbeta-CyclodextrinsCalciumCaveolin 3CholesterolGene ExpressionMiceMolecular ImagingMyocardiumMyocytes, CardiacSarcoplasmic Reticulumbeta-CyclodextrinsCalciumCaveolin 3Cholesterolmethyl-beta-cyclodextrinCa(2+) handlingCardiomyocytesCholesterolIntercalated discsT-tubules

Identifiers

PMID27255730
PMCPMC5002380
OpenAlexW2410333440

What OpenQuestion holds

Textmetadata
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.