title: Conditional mineralocorticoid receptor expression in the heart leads to life-threatening arrhythmias.
abstract: BACKGROUND
  Life-threatening cardiac arrhythmia is a major source of mortality worldwide. Besides rare inherited monogenic diseases such as long-QT or Brugada syndromes, which reflect abnormalities in ion fluxes across cardiac ion channels as a final common pathway, arrhythmias are most frequently acquired and associated with heart disease. The mineralocorticoid hormone aldosterone is an important contributor to morbidity and mortality in heart failure, but its mechanisms of action are incompletely understood.
  
  
  RESULTS
  To specifically assess the role of the mineralocorticoid receptor (MR) in the heart, in the absence of changes in aldosteronemia, we generated a transgenic mouse model with conditional cardiac-specific overexpression of the human MR. Mice exhibit a high rate of death prevented by spironolactone, an MR antagonist used in human therapy. Cardiac MR overexpression led to ion channel remodeling, resulting in prolonged ventricular repolarization at both the cellular and integrated levels and in severe ventricular arrhythmias.
  
  
  CONCLUSIONS
  Our results indicate that cardiac MR triggers cardiac arrhythmias, suggesting novel opportunities for prevention of arrhythmia-related sudden death.
authors.affiliation: INSERM AVENIR, Collège de France, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Ouvrard-Pascaud
authors.forename: Yannis
authors.initials: Y
authors.lastname: Sainte-Marie
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bénitah
authors.forename: Romain
authors.initials: R
authors.lastname: Perrier
authors.forename: Christelle
authors.initials: C
authors.lastname: Soukaseum
authors.forename: Aurelie
authors.initials: A
authors.lastname: Nguyen Dinh Cat
authors.forename: Anne
authors.initials: A
authors.lastname: Royer
authors.forename: Khai
authors.initials: K
authors.lastname: Le Quang
authors.forename: Flavien
authors.initials: F
authors.lastname: Charpentier
authors.forename: Sophie
authors.initials: S
authors.lastname: Demolombe
authors.forename: Fatima
authors.initials: F
authors.lastname: Mechta-Grigoriou
authors.forename: Ahmed T
authors.initials: AT
authors.lastname: Beggah
authors.forename: Pierre
authors.initials: P
authors.lastname: Maison-Blanche
authors.forename: Marie-Edith
authors.initials: ME
authors.lastname: Oblin
authors.forename: Claude
authors.initials: C
authors.lastname: Delcayre
authors.forename: Glenn I
authors.initials: GI
authors.lastname: Fishman
authors.forename: Nicolette
authors.initials: N
authors.lastname: Farman
authors.forename: Brigitte
authors.initials: B
authors.lastname: Escoubet
authors.forename: Frederic
authors.initials: F
authors.lastname: Jaisser
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D016638:Critical Illness; D003645:Death, Sudden; D004195:Disease Models, Animal; D004562:Electrocardiography; D004594:Electrophysiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007473:Ion Channels; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018161:Receptors, Mineralocorticoid / Q000235:genetics*
chemical_list: D007473:Ion Channels; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D002118:Calcium