title: Critical role for stromal interaction molecule 1 in cardiac hypertrophy.
abstract: BACKGROUND
  Cardiomyocytes use Ca2+ not only in excitation-contraction coupling but also as a signaling molecule promoting, for example, cardiac hypertrophy. It is largely unclear how Ca2+ triggers signaling in cardiomyocytes in the presence of the rapid and large Ca2+ fluctuations that occur during excitation-contraction coupling. A potential route is store-operated Ca2+ entry, a drug-inducible mechanism for Ca2+ signaling that requires stromal interaction molecule 1 (STIM1). Store-operated Ca2+ entry can also be induced in cardiomyocytes, which prompted us to study STIM1-dependent Ca2+ entry with respect to cardiac hypertrophy in vitro and in vivo.
  
  
  RESULTS
  Consistent with earlier reports, we found drug-inducible store-operated Ca2+ entry in neonatal rat cardiomyocytes, which was dependent on STIM1. Although this STIM1-dependent, drug-inducible store-operated Ca2+ entry was only marginal in adult cardiomyocytes isolated from control hearts, it increased significantly in cardiomyocytes isolated from adult rats that had developed compensated cardiac hypertrophy after abdominal aortic banding. Moreover, we detected an inwardly rectifying current in hypertrophic cardiomyocytes that occurs under native conditions (i.e., in the absence of drug-induced store depletion) and is dependent on STIM1. By manipulating its expression, we found STIM1 to be both sufficient and necessary for cardiomyocyte hypertrophy in vitro and in the adult heart in vivo. Stim1 silencing by adeno-associated viruses of serotype 9-mediated gene transfer protected rats from pressure overload-induced cardiac hypertrophy.
  
  
  CONCLUSIONS
  By controlling a previously unrecognized sarcolemmal current, STIM1 promotes cardiac hypertrophy.
authors.affiliation: PhD.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.forename: Jérémy
authors.initials: J
authors.lastname: Fauconnier
authors.forename: Deepak
authors.initials: D
authors.lastname: Ramanujam
authors.forename: Antoine
authors.initials: A
authors.lastname: Chaanine
authors.forename: Fleur
authors.initials: F
authors.lastname: Aubart
authors.forename: Yassine
authors.initials: Y
authors.lastname: Sassi
authors.forename: Sabine
authors.initials: S
authors.lastname: Merkle
authors.forename: Olivier
authors.initials: O
authors.lastname: Cazorla
authors.forename: Aude
authors.initials: A
authors.lastname: Ouillé
authors.forename: Morgan
authors.initials: M
authors.lastname: Dupuis
authors.forename: Lahouaria
authors.initials: L
authors.lastname: Hadri
authors.forename: Dongtak
authors.initials: D
authors.lastname: Jeong
authors.forename: Silke
authors.initials: S
authors.lastname: Mühlstedt
authors.forename: Joachim
authors.initials: J
authors.lastname: Schmitt
authors.forename: Attila
authors.initials: A
authors.lastname: Braun
authors.forename: Ludovic
authors.initials: L
authors.lastname: Bénard
authors.forename: Youakim
authors.initials: Y
authors.lastname: Saliba
authors.forename: Bernhard
authors.initials: B
authors.lastname: Laggerbauer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.forename: Alain
authors.initials: A
authors.lastname: Lacampagne
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lompré
authors.forename: Stefan
authors.initials: S
authors.lastname: Engelhardt
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D010726:Phosphodiesterase Inhibitors; C100757:Stim1 protein, mouse; C518857:Stim1 protein, rat; D000071737:Stromal Interaction Molecule 1; D002110:Caffeine; D019284:Thapsigargin; D002118:Calcium