Evidence map›Paper›PMID 17440815›Full record

ArticleApoptosis : an international journal on programmed cell death2007

Homocysteine affects cardiomyocyte viability: concentration-dependent effects on reversible flip-flop, apoptosis and necrosis.

Jessica A Sipkens, Paul A J Krijnen, Christof Meischl, Saskia A G M Cillessen, Yvo M Smulders, Desirée E C Smith, Cindy P E Giroth, Marieke D Spreeuwenberg, René J P Musters, Alice Muller and 6 more

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In one paragraph

Article in Apoptosis : an international journal on programmed cell death, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

19 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
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  5. Homocysteine and Mitochondria in Cardiovascular and Cerebrovascular Systems.International journal of molecular sciences · 2020
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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

16 authors at 3 institutions in 1 country.

Jessica A SipkensDepartment of Pathology, VU University Medical Centre, Room 0E46, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands. j.sipkens@vumc.nl
Paul A J Krijnen
Christof Meischl
Saskia A G M Cillessen
Yvo M Smulders
Desirée E C Smith
Cindy P E Giroth
Marieke D Spreeuwenberg
René J P Musters
Alice Muller
Cornelis Jakobs
Dirk Roos
Coen D A Stehouwer
Jan A Rauwerda
Victor W M van Hinsbergh
Hans W M Niessen
Amsterdam UMC Location VUmc · NLMaastricht University Medical Centre · NLUniversity of Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHyperhomocysteinaemia (HHC) is thought to be a risk factor for cardiovascular disease including heart failure. While numerous studies have analyzed the role of homocysteine (Hcy) in the vasculature, only a few studies investigated the role of Hcy in the heart. Therefore we have analyzed the effects of Hcy on isolated cardiomyocytes.

methodsH9c2 cells (rat cardiomyoblast cells) and adult rat cardiomyocytes were incubated with Hcy and were analyzed for cell viability. Furthermore, we determined the effects of Hcy on intracellular mediators related to cell viability in cardiomyocytes, namely NOX2, reactive oxygen species (ROS), mitochondrial membrane potential (DeltaPsi (m)) and ATP concentrations.

resultsWe found that incubation of H9c2 cells with 0.1 mM D,L-Hcy (= 60 microM L-Hcy) resulted in an increase of DeltaPsi (m) as well as ATP concentrations. 1.1 mM D,L-Hcy (= 460 microM L-Hcy) induced reversible flip-flop of the plasma membrane phospholipids, but not apoptosis. Incubation with 2.73 mM D,L-Hcy (= 1.18 mM L-Hcy) induced apoptosis and necrosis. This loss of cell viability was accompanied by a thread-to-grain transition of the mitochondrial reticulum, ATP depletion and nuclear NOX2 expression coinciding with ROS production as evident from the presence of nitrotyrosin residues. Notably, only at this concentration we found a significant increase in S-adenosylhomocysteine which is considered the primary culprit in HHC.

conclusionWe found concentration-dependent effects of Hcy in cardiomyocytes, varying from induction of reversible flip-flop of the plasma membrane phospholipids, to apoptosis and necrosis.

Indexed as

Adenosine TriphosphateAnimalsApoptosisCaspase 3Cell MembraneCells, CulturedCell SurvivalDose-Response Relationship, DrugGene Expression RegulationHomocysteineMembrane FluidityMembrane GlycoproteinsMembrane Potential, MitochondrialMitochondria, HeartModels, BiologicalMyocytes, CardiacAdenosine TriphosphateCaspase 3Cybb protein, ratHomocysteineMembrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesPhospholipidsS-AdenosylhomocysteineS-Adenosylmethionine

Identifiers

PMID17440815
PMCPMC1914234
OpenAlexW1977377731

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.