Evidence map›Paper›PMID 26936863›Full record

ArticleCirculation2016

Cardiac Stim1 Silencing Impairs Adaptive Hypertrophy and Promotes Heart Failure Through Inactivation of mTORC2/Akt Signaling.

Ludovic Bénard, Jae Gyun Oh, Marine Cacheux, Ahyoung Lee, Mathieu Nonnenmacher, Daniel S Matasic, Erik Kohlbrenner, Changwon Kho, Catherine Pavoine, Roger J Hajjar and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
8.7field-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

62 citing papers in PubMed, 92 citations in OpenAlex.

  1. Article
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  6. Article
  7. Article
  8. Review
  9. Role of STIM1 in the Regulation of Cardiac Energy Substrate Preference.International journal of molecular sciences · 2023
    Review
  10. Article
  11. Article
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  13. Review
  14. Article
  15. Article
  16. Analysis ofAmerican journal of physiology. Heart and circulatory physiology · 2022
    Article
  17. Review
  18. Review
  19. Article
  20. Article

2 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

11 authors at 1 institution in 1 country.

Ludovic BénardFrom Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.B., J.G.O., M.C., A.L., M.N., D.S.M., E.K., C.W.K., R.J.H., J.-S.H.); and Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France (C.P., J.-S.H.).
Jae Gyun OhFrom Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.B., J.G.O., M.C., A.L., M.N., D.S.M., E.K., C.W.K., R.J.H., J.-S.H.); and Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France (C.P., J.-S.H.).
Marine CacheuxFrom Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.B., J.G.O., M.C., A.L., M.N., D.S.M., E.K., C.W.K., R.J.H., J.-S.H.); and Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France (C.P., J.-S.H.).
Ahyoung LeeFrom Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.B., J.G.O., M.C., A.L., M.N., D.S.M., E.K., C.W.K., R.J.H., J.-S.H.); and Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France (C.P., J.-S.H.).
Mathieu NonnenmacherFrom Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.B., J.G.O., M.C., A.L., M.N., D.S.M., E.K., C.W.K., R.J.H., J.-S.H.); and Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France (C.P., J.-S.H.).
Daniel S MatasicFrom Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.B., J.G.O., M.C., A.L., M.N., D.S.M., E.K., C.W.K., R.J.H., J.-S.H.); and Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France (C.P., J.-S.H.).
Erik KohlbrennerFrom Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.B., J.G.O., M.C., A.L., M.N., D.S.M., E.K., C.W.K., R.J.H., J.-S.H.); and Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France (C.P., J.-S.H.).
Changwon KhoFrom Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.B., J.G.O., M.C., A.L., M.N., D.S.M., E.K., C.W.K., R.J.H., J.-S.H.); and Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France (C.P., J.-S.H.).
Catherine PavoineFrom Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.B., J.G.O., M.C., A.L., M.N., D.S.M., E.K., C.W.K., R.J.H., J.-S.H.); and Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France (C.P., J.-S.H.).
Roger J HajjarFrom Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.B., J.G.O., M.C., A.L., M.N., D.S.M., E.K., C.W.K., R.J.H., J.-S.H.); and Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France (C.P., J.-S.H.).
Jean-Sébastien HulotFrom Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.B., J.G.O., M.C., A.L., M.N., D.S.M., E.K., C.W.K., R.J.H., J.-S.H.); and Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France (C.P., J.-S.H.). jean.hulot@mssm.edu.
Sorbonne Université · FR

Funding

Targeting Abnormal Calcium Cycling Using Novel Gene Therapy VectorsR01HL119046 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKAR, FADI GABRIEL, HAJJAR, ROGER J. · 2014 to 2017
$2.9M
Treating Ventricle and Valve: New Synergies for Ischemic LV Remodeling with MRR01HL128099 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AKAR, FADI GABRIEL, LEVINE, ROBERT A · 2016 to 2019
$2.8M
Role of miR25 in Heart FailureR01HL128072 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J., MERCOLA, MARK · 2015 to 2018
$2.5M
Role of STIM1 in cardiac hypertrophy and heart failureR01HL113497 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKAR, FADI GABRIEL · 2012 to 2016
$2.1M
Targeting Calcium Cycling in Pre-Clinical Model CardiacR01HL083156 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI HAJJAR, ROGER J. · 2006 to 2010
$1.7M
C-TRIP: Targeted Gene Therapy for the Treatment of Heart Failure (P20)P20HL100396 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J. · 2010 to 2011
$1.7M
Regression of cardiac hypertrophyR01HL093183 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J. · 2009 to 2010
$1.1M
The Role of Post-translational Acetylation in SERCA2a-related Cardiac DysfunctionR00HL116645 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KHO, CHANGWON · 2015 to 2017
$747k
NHLBI NIH HHS HHSN268201000045CNHLBI NIH HHS HL083156NHLBI NIH HHS HL093183NHLBI NIH HHS HL119046NHLBI NIH HHS P20 HL100396NHLBI NIH HHS P20HL100396NHLBI NIH HHS R00 HL116645NHLBI NIH HHS R00HL116645NHLBI NIH HHS R01 HL083156NHLBI NIH HHS R01 HL093183NHLBI NIH HHS R01 HL113497NHLBI NIH HHS R01 HL119046NHLBI NIH HHS R01 HL128072NHLBI NIH HHS R01 HL128099PHS HHS HHSN268201000045C
6 · The paper itself

Abstract

backgroundStromal interaction molecule 1 (STIM1) is a dynamic calcium signal transducer implicated in hypertrophic growth of cardiomyocytes. STIM1 is thought to act as an initiator of cardiac hypertrophic response at the level of the sarcolemma, but the pathways underpinning this effect have not been examined. METHODS AND

resultsTo determine the mechanistic role of STIM1 in cardiac hypertrophy and during the transition to heart failure, we manipulated STIM1 expression in mice cardiomyocytes by using in vivo gene delivery of specific short hairpin RNAs. In 3 different models, we found that Stim1 silencing prevents the development of pressure overload-induced hypertrophy but also reverses preestablished cardiac hypertrophy. Reduction in STIM1 expression promoted a rapid transition to heart failure. We further showed that Stim1 silencing resulted in enhanced activity of the antihypertrophic and proapoptotic GSK-3β molecule. Pharmacological inhibition of glycogen synthase kinase-3 was sufficient to reverse the cardiac phenotype observed after Stim1 silencing. At the level of ventricular myocytes, Stim1 silencing or inhibition abrogated the capacity for phosphorylation of Akt(S473), a hydrophobic motif of Akt that is directly phosphorylated by mTOR complex 2. We found that Stim1 silencing directly impaired mTOR complex 2 kinase activity, which was supported by a direct interaction between STIM1 and Rictor, a specific component of mTOR complex 2.

conclusionsThese data support a model whereby STIM1 is critical to deactivate a key negative regulator of cardiac hypertrophy. In cardiomyocytes, STIM1 acts by tuning Akt kinase activity through activation of mTOR complex 2, which further results in repression of GSK-3β activity.

Indexed as

Amino Acid MotifsAnimalsCalcium ChannelsCalcium SignalingCardiomegalyCarrier ProteinsDisease Models, AnimalGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHeart FailureMaleMechanistic Target of Rapamycin Complex 2MiceMice, Inbred C57BLMultiprotein ComplexesMyocytes, CardiacAkt1 protein, mouseCalcium ChannelsCarrier ProteinsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGsk3b protein, mouseMechanistic Target of Rapamycin Complex 2Multiprotein ComplexesProto-Oncogene Proteins c-aktRapamycin-Insensitive Companion of mTOR Proteinrictor protein, mouseRNA, Small InterferingStim1 protein, mouseStromal Interaction Molecule 1TOR Serine-Threonine Kinasescalciumgenetic therapyheart failureStim1 protein, mouseTOR complex 2

Identifiers

PMID26936863
PMCPMC4829441
OpenAlexW2299887796

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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.