title: Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology.
abstract: BACKGROUND
  The molecular mechanisms governing right atrial (RA) and ventricular (RV) hypertrophy and failure in chronic pulmonary hypertension (CPH) remain unclear. The purpose of this investigation was to characterize RA and RV protein changes in CPH and determine their adaptive versus maladaptive role on hypertrophic development.
  
  
  METHODS
  Nine dogs underwent sternotomy and RA injection with 3 mg/kg dehydromonocrotaline (DMCT) to induce CPH (n=5) or sternotomy without DMCT (n=4). At 8-10 weeks, RA and RV proteomic analyses were completed after trypsinization of cut 2-D gel electrophoresis spots and peptide sequencing using mass spectrometry.
  
  
  RESULTS
  In the RV, 13 protein spots were significantly altered with DMCT compared to Sham. Downregulated RV proteins included contractile elements: troponin T and C (-1.6 fold change), myosin regulatory light chain 2 (-1.9), cellular energetics modifier: fatty-acid binding protein (-1.5), and (3) ROS scavenger: superoxide dismutase 1 (-1.7). Conversely, beta-myosin heavy chain was upregulated (+1.7). In the RA, 22 proteins spots were altered including the following downregulated proteins contractile elements: tropomyosin 1 alpha chain (-1.9), cellular energetic proteins: ATP synthase (-1.5), fatty-acid binding protein (-2.5), and (3) polyubiquitin (-3.5). Crystallin alpha B (hypertrophy inhibitor) was upregulated in both the RV (+2.2) and RA (+2.6).
  
  
  CONCLUSIONS
  In early stage hypertrophy there is adaptive upregulation of major RA and RV contractile substituents and attenuation of the hypertrophic response. However, there are multiple indices of maladaptive pathology including considerable cellular stress associated with aberrancy of actin machinery activity, decreased efficiency of energy utilization, and potentially decreased protein quality control.
authors.affiliation: Division of Cardiothoracic Surgery and Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Abdulhameed
authors.initials: A
authors.lastname: Aziz
authors.affiliation: Division of Cardiothoracic Surgery and Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Anson M
authors.initials: AM
authors.lastname: Lee
authors.affiliation: Division of Cardiothoracic Surgery and Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Nneka N
authors.initials: NN
authors.lastname: Ufere
authors.affiliation: Division of Cardiothoracic Surgery and Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Damiano
authors.affiliation: Division of Cardiothoracic Surgery and Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Reid R
authors.initials: RR
authors.lastname: Townsend
authors.affiliation: Division of Cardiothoracic Surgery and Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Moon
keywords: Hypertrophy; Protein expression; Proteome; Proteomics; Pulmonary hypertension; Right heart