Evidence map›Paper›PMID 25648353›Full record

ArticleCirculation. Arrhythmia and electrophysiology2015

Role of mutation and pharmacologic block of human KCNH2 in vasculogenesis and fetal mortality: partial rescue by transforming growth factor-β.

Guoqi Teng, Xiang Zhao, James P Lees-Miller, Darrell Belke, Chunhua Shi, Yongxiang Chen, Edward R O'Brien, Paul W Fedak, Nathan Bracey, James C Cross and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Circulation. Arrhythmia and electrophysiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

9 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  5. Article
  6. Ion Channels and Transporters in Muscle Cell Differentiation.International journal of molecular sciences · 2021
    Review
  7. Article
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Guoqi TengFrom the Libin Cardiovascular Institute, Faculty of Medicine (G.T., J.P.L.-M., D.B., C.S., Y.C., E.R.O'B., P.W.F., N.B., H.J.D.) and Department of Comparative Biology and Experimental Medicine and Faculty of Veterinary Medicine (X.Z., J.C.C.), University of Calgary, Calgary, Alberta, Canada.
Xiang ZhaoFrom the Libin Cardiovascular Institute, Faculty of Medicine (G.T., J.P.L.-M., D.B., C.S., Y.C., E.R.O'B., P.W.F., N.B., H.J.D.) and Department of Comparative Biology and Experimental Medicine and Faculty of Veterinary Medicine (X.Z., J.C.C.), University of Calgary, Calgary, Alberta, Canada.
James P Lees-MillerFrom the Libin Cardiovascular Institute, Faculty of Medicine (G.T., J.P.L.-M., D.B., C.S., Y.C., E.R.O'B., P.W.F., N.B., H.J.D.) and Department of Comparative Biology and Experimental Medicine and Faculty of Veterinary Medicine (X.Z., J.C.C.), University of Calgary, Calgary, Alberta, Canada.
Darrell BelkeFrom the Libin Cardiovascular Institute, Faculty of Medicine (G.T., J.P.L.-M., D.B., C.S., Y.C., E.R.O'B., P.W.F., N.B., H.J.D.) and Department of Comparative Biology and Experimental Medicine and Faculty of Veterinary Medicine (X.Z., J.C.C.), University of Calgary, Calgary, Alberta, Canada.
Chunhua ShiFrom the Libin Cardiovascular Institute, Faculty of Medicine (G.T., J.P.L.-M., D.B., C.S., Y.C., E.R.O'B., P.W.F., N.B., H.J.D.) and Department of Comparative Biology and Experimental Medicine and Faculty of Veterinary Medicine (X.Z., J.C.C.), University of Calgary, Calgary, Alberta, Canada.
Yongxiang ChenFrom the Libin Cardiovascular Institute, Faculty of Medicine (G.T., J.P.L.-M., D.B., C.S., Y.C., E.R.O'B., P.W.F., N.B., H.J.D.) and Department of Comparative Biology and Experimental Medicine and Faculty of Veterinary Medicine (X.Z., J.C.C.), University of Calgary, Calgary, Alberta, Canada.
Edward R O'BrienFrom the Libin Cardiovascular Institute, Faculty of Medicine (G.T., J.P.L.-M., D.B., C.S., Y.C., E.R.O'B., P.W.F., N.B., H.J.D.) and Department of Comparative Biology and Experimental Medicine and Faculty of Veterinary Medicine (X.Z., J.C.C.), University of Calgary, Calgary, Alberta, Canada.
Paul W FedakFrom the Libin Cardiovascular Institute, Faculty of Medicine (G.T., J.P.L.-M., D.B., C.S., Y.C., E.R.O'B., P.W.F., N.B., H.J.D.) and Department of Comparative Biology and Experimental Medicine and Faculty of Veterinary Medicine (X.Z., J.C.C.), University of Calgary, Calgary, Alberta, Canada.
Nathan BraceyFrom the Libin Cardiovascular Institute, Faculty of Medicine (G.T., J.P.L.-M., D.B., C.S., Y.C., E.R.O'B., P.W.F., N.B., H.J.D.) and Department of Comparative Biology and Experimental Medicine and Faculty of Veterinary Medicine (X.Z., J.C.C.), University of Calgary, Calgary, Alberta, Canada.
James C CrossFrom the Libin Cardiovascular Institute, Faculty of Medicine (G.T., J.P.L.-M., D.B., C.S., Y.C., E.R.O'B., P.W.F., N.B., H.J.D.) and Department of Comparative Biology and Experimental Medicine and Faculty of Veterinary Medicine (X.Z., J.C.C.), University of Calgary, Calgary, Alberta, Canada.
Henry J DuffFrom the Libin Cardiovascular Institute, Faculty of Medicine (G.T., J.P.L.-M., D.B., C.S., Y.C., E.R.O'B., P.W.F., N.B., H.J.D.) and Department of Comparative Biology and Experimental Medicine and Faculty of Veterinary Medicine (X.Z., J.C.C.), University of Calgary, Calgary, Alberta, Canada. hduff@ucalgary.ca.
Libin Cardiovascular Institute of Alberta · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

backgroundN629D KCNH2 is a human missense long-QT2 mutation. Previously, we reported that the N629D/N629D mutation embryos disrupted cardiac looping, right ventricle development, and ablated IKr activity at E9.5. The present study evaluates the role of KCNH2 in vasculogenesis. METHODS AND

resultsN629D/N629D yolk sac vessels and aorta consist of sinusoids without normal arborization. Isolated E9.5 +/+ first branchial arches showed normal outgrowth of mouse ERG-positive/α-smooth muscle actin coimmunolocalized cells; however, outgrowth was grossly reduced in N629D/N629D. N629D/N629D aortas showed fewer α-smooth muscle actin positive cells that were not coimmunolocalized with mouse ERG cells. Transforming growth factor-β treatment of isolated N629D/N629D embryoid bodies partially rescued this phenotype. Cultured N629D/N629D embryos recapitulate the same cardiovascular phenotypes as seen in vivo. Transforming growth factor-β treatment significantly rescued these embryonic phenotypes. Both in vivo and in vitro, dofetilide treatment, over a narrow window of time, entirely recapitulated the N629D/N629D fetal phenotypes. Exogenous transforming growth factor-β treatment also rescued the dofetilide-induced phenotype toward normal.

conclusionsLoss of function of KCNH2 mutations results in defects in cardiogenesis and vasculogenesis. Because many medications inadvertently block the KCNH2 potassium current, these novel findings seem to have clinical relevance.

Indexed as

Fetal DeathMutation, MissenseAbnormalities, Drug-InducedAnimalsCells, CulturedEmbryo Culture TechniquesEmbryonic Stem CellsERG1 Potassium ChannelEther-A-Go-Go Potassium ChannelsGene Expression Regulation, DevelopmentalGenotypeHeart Defects, CongenitalHumansMice, 129 StrainMice, TransgenicMorphogenesisdofetilideERG1 Potassium ChannelEther-A-Go-Go Potassium ChannelsKCNH2 protein, humanKcnh2 protein, mousePhenethylaminesPotassium Channel BlockersSulfonamidesTransforming Growth Factor betaaortaembryonic developmentgene targetingmiceorganogenesispotassium channelstransforming growth factor beta

Identifiers

PMID25648353
OpenAlexW2549301328

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.