title: Altered protein levels in the isolated extracellular matrix of failing human hearts with dilated cardiomyopathy.
abstract: Dilated cardiomyopathy (DCM) is associated with extensive pathological cardiac remodeling and involves numerous changes in the protein expression profile of the extracellular matrix of the heart. We obtained seven human, end-stage, failing hearts with DCM (DCM-failing) and nine human, nonfailing donor hearts and compared their extracellular matrix protein profiles. We first showed that the DCM-failing hearts had indeed undergone extensive remodeling of the left ventricle myocardium relative to nonfailing hearts. We then isolated the extracellular matrix from a subset of these hearts and performed a proteomic analysis on the isolated matrices. We found that the levels of 26 structural proteins were altered in the DCM-failing isolated cardiac extracellular matrix compared to nonfailing isolated cardiac extracellular matrix. Overall, most of the extracellular matrix proteins showed reduced levels in the DCM-failing hearts, while all of the contractile proteins showed increased levels. There was a mixture of increased and decreased levels of cytoskeletal and nuclear transport proteins. Using immunoprobing, we verified that collagen IV (α2and α6isoforms), zyxin, and myomesin protein levels were reduced in the DCM-failing hearts. We expect that these data will add to the understanding of the pathology associated with heart failure with DCM.
authors.affiliation: The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, MSC09 5360, 1 University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: joshdeaguero@unm.edu.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: DeAguero
authors.affiliation: The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, MSC09 5360, 1 University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: emckown@salud.unm.edu.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: McKown
authors.affiliation: The Ohio State University Mass Spectrometry and Proteomics Facility, Campus Chemical Instrument Center, 460 W. 12th Ave., Room 250 Biomedical Research Tower, Columbus, OH 43210, USA. Electronic address: zhang.287@osu.edu.
authors.forename: Liwen
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Ohio State University Mass Spectrometry and Proteomics Facility, Campus Chemical Instrument Center, 460 W. 12th Ave., Room 250 Biomedical Research Tower, Columbus, OH 43210, USA. Electronic address: keirsey.1@osu.edu.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Keirsey
authors.affiliation: The University of New Mexico School of Medicine, Department of Pathology, MSC08 4640, 1 University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: efischer@salud.unm.edu.
authors.forename: Edgar G
authors.initials: EG
authors.lastname: Fischer
authors.affiliation: The University of New Mexico School of Medicine, Department of Pathology, MSC08 4640, 1 University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: vgsamedi@salud.unm.edu.
authors.forename: Von G
authors.initials: VG
authors.lastname: Samedi
authors.affiliation: The Ohio State University College of Medicine, Department of Physiology and Cell Biology and the Davis Heart Lung Research Institute, 200 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210. Electronic address: Benjamin.canan@osumc.edu.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Canan
authors.affiliation: The Ohio State University College of Medicine, Department of Surgery and the Davis Heart Lung Research Institute, Richard M. Ross Heart Hospital, 452 West 10th Ave., Columbus, OH 43210. Electronic address: Kilic.9@osu.edu.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Kilic
authors.affiliation: The Ohio State University College of Medicine, Department of Physiology and Cell Biology and the Davis Heart Lung Research Institute, 200 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210. Electronic address: janssen.10@osu.edu.
authors.forename: Paul M L
authors.initials: PM
authors.lastname: Janssen
authors.affiliation: The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, MSC09 5360, 1 University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: ddelfin@salud.unm.edu.
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Delfín
mesh_terms: D000328:Adult; D000368:Aged; D064752:Atrial Remodeling; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000473:pathology; D002853:Chromatography, Liquid; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics
keywords: Dilated cardiomyopathy; Extracellular matrix; Heart failure; Proteomics