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Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology

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...

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Autores principales: Aziz, Abdulhameed, Lee, Anson M., Ufere, Nneka N., Damiano, Ralph J., Townsend, Reid R, Moon, Marc R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523278/
https://www.ncbi.nlm.nih.gov/pubmed/26246959
http://dx.doi.org/10.4172/2161-105X.1000241
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author Aziz, Abdulhameed
Lee, Anson M.
Ufere, Nneka N.
Damiano, Ralph J.
Townsend, Reid R
Moon, Marc R.
author_facet Aziz, Abdulhameed
Lee, Anson M.
Ufere, Nneka N.
Damiano, Ralph J.
Townsend, Reid R
Moon, Marc R.
author_sort Aziz, Abdulhameed
collection PubMed
description 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.
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spelling pubmed-45232782015-08-03 Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology Aziz, Abdulhameed Lee, Anson M. Ufere, Nneka N. Damiano, Ralph J. Townsend, Reid R Moon, Marc R. J Pulm Respir Med Article 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. 2015-01-23 2015 /pmc/articles/PMC4523278/ /pubmed/26246959 http://dx.doi.org/10.4172/2161-105X.1000241 Text en http://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Article
Aziz, Abdulhameed
Lee, Anson M.
Ufere, Nneka N.
Damiano, Ralph J.
Townsend, Reid R
Moon, Marc R.
Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology
title Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology
title_full Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology
title_fullStr Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology
title_full_unstemmed Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology
title_short Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology
title_sort proteomic profiling of early chronic pulmonary hypertension: evidence for both adaptive and maladaptive pathology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523278/
https://www.ncbi.nlm.nih.gov/pubmed/26246959
http://dx.doi.org/10.4172/2161-105X.1000241
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