title: Endoplasmic reticulum stress induces different molecular structural alterations in human dilated and ischemic cardiomyopathy.
abstract: BACKGROUND
  The endoplasmic reticulum (ER) is a multifunctional organelle responsible for the synthesis and folding of proteins as well as for signalling and calcium storage, that has been linked to the contraction-relaxation process. Perturbations of its homeostasis activate a stress response in diseases such as heart failure (HF). To elucidate the alterations in ER molecular components, we analyze the levels of ER stress and structure proteins in human dilated (DCM) and ischemic (ICM) cardiomyopathies, and its relationship with patient's functional status.
  
  
  RESULTS
  We examined 52 explanted human hearts from DCM (n = 21) and ICM (n = 21) subjects and 10 non-failing hearts as controls. Our results showed specific changes in stress (IRE1, p<0.05; p-IRE1, p<0.05) and structural (Reticulon 1, p<0.01) protein levels. The stress proteins GRP78, XBP1 and ATF6 as well as the structural proteins RRBP1, kinectin, and Nogo A and B, were upregulated in both DCM and ICM patients. Immunofluorescence results were concordant with quantified Western blot levels. Moreover, we show a novel relationship between stress and structural proteins. RRBP1, involved in procollagen synthesis and remodeling, was related with left ventricular function.
  
  
  CONCLUSIONS
  In the present study, we report the existence of alterations in ER stress response and shaping proteins. We show a plausible effect of the ER stress on ER structure in a suitable sample of DCM and ICM subjects. Patients with higher values of RRBP1 had worse left ventricular function.
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Roselló-Lletí
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Tarazón
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain.
authors.forename: Maria Micaela
authors.initials: MM
authors.lastname: Molina-Navarro
authors.affiliation: Heart Failure and Transplantation Unit, Cardiology Department, La Fe University Hospital, Valencia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Dolz
authors.affiliation: Cellular and Molecular Cardiology Research Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: González-Juanatey
authors.affiliation: Cellular and Molecular Cardiology Research Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Lago
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain.
authors.forename: Jose David
authors.initials: JD
authors.lastname: Montoro-Mateos
authors.affiliation: Heart Failure and Transplantation Unit, Cardiology Department, La Fe University Hospital, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Salvador
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivera
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portolés
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D021381:Protein Transport; D020543:Proteome
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D020543:Proteome