title: Proteomic identification of putative biomarkers for early detection of sudden cardiac death in a family with a LMNA gene mutation causing dilated cardiomyopathy.
abstract: Dilated cardiomyopathy (DCM) is a severe heart disease characterized by progressive ventricular dilation and impaired systolic function of the left ventricle. We recently identified a novel pathogenic mutation in the LMNA gene in a family affected by DCM showing sudden death background. We now aimed to identify potential biomarkers of disease status, as well as sudden death predictors, in members of this family. We analysed plasma samples from 14 family members carrying the mutation, four of which (with relevant clinical symptoms) were chosen for the proteomic analysis. Plasma samples from these four patients and from four sex- and age-matched healthy controls were processed for their enrichment in low- and medium-abundance proteins (ProteoMiner™) prior to proteomic analysis by 2D-DIGE and MS. 111 spots were found to be differentially regulated between mutation carriers and control groups, 83 of which were successfully identified by MS, corresponding to 41 different ORFs. Some proteins of interest were validated either by turbidimetry or western blot in family members and healthy controls. Actin, alpha-1-antytripsin, clusterin, vitamin-D binding protein and antithrombin-III showed increased levels in plasma from the diseased group. We suggest following these proteins as putative biomarkers for the evaluation of DCM status in LMNA mutation carriers.
  
  
  
  We developed a proteomic analysis of plasma samples from a family showing history of dilated cardiomyopathy caused by a LMNA mutation, which may lead to premature death or cardiac transplant. We identified a number of proteins augmented in mutation carriers that could be followed as potential biomarkers for dilated cardiomyopathy on these patients.
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidad de Santiago de Compostela, and Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain; Departament of Pharmacology, Faculty of Pharmacy, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Izquierdo
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidad de Santiago de Compostela, and Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Rosa
authors.affiliation: Proteomic Unit, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: Susana Belén
authors.initials: SB
authors.lastname: Bravo
authors.affiliation: Mass Spectrometry and Proteomic Unit, Rede de Infraestructuras de Apoio á Investigación e ao Desenvolvemento Tecnolóxico (RIAIDT), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Guitián
authors.affiliation: Cardiovascular Genetics Center, IDIBGI, University of Girona, Girona, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pérez-Serra
authors.affiliation: Cardiovascular Genetics Center, IDIBGI, University of Girona, Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Campuzano
authors.affiliation: Cardiovascular Genetics Center, IDIBGI, University of Girona, Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain; Cardiac Genetics Unit, Hospital Josep Trueta, University of Girona, Girona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
authors.affiliation: Medicine Department, School of Medicine, Universidad de Cádiz, Spain.
authors.forename: Alipio
authors.initials: A
authors.lastname: Mangas
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidad de Santiago de Compostela, and Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain; Departament of Pharmacology, Faculty of Pharmacy, Universidade de Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: angel.garcia@usc.es.
authors.forename: Ángel
authors.initials: Á
authors.lastname: García
authors.affiliation: Medicine Department, School of Medicine, Universidad de Cádiz, Spain. Electronic address: rociotorogreen@gmail.com.
authors.forename: Rocio
authors.initials: R
authors.lastname: Toro
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac / Q000209:etiology* / Q000517:prevention & control; D005192:Family Health; D005260:Female; D006801:Humans; D007223:Infant; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D040901:Proteomics / Q000379:methods; D057825:Two-Dimensional Difference Gel Electrophoresis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D034904:Lamin Type A
keywords: Dilated cardiomyopathy; LMNA; Plasma biomarkers; Sudden cardiac death