Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive PathologyAbdulhameed Aziz, Anson M. Lee, Nneka N. Ufere, Ralph J. Damiano, Reid Townsend R and Marc R. Moon*
Division of Cardiothoracic Surgery and Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
- *Corresponding Author:
- Marc R. Moon, MD
Division of Cardiothoracic Surgery
Washington University School of Medicine
660 S. Euclid Ave., Box 8234 St. Louis, Missouri, USA
Tel: (314) 362-0993
Fax: (314) 747-0917
E-mail: [email protected]
Received date: September 23, 2014; Accepted date: January 13, 2015; Published date: January 23, 2015
Citation: Aziz A, Lee AM, Ufere NN, Damiano RJ, Townsend RR, et al. (2015) Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology. J Pulm Respir Med 5:241. doi:10.4172/2161-105X.1000241
Copyright: © 2015 Aziz A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.