Skeletal muscle proteomic signature and metabolic impairment in pulmonary hypertension
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| 024 | 7 | 0 | |a 10.1007/s00109-014-1244-0 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00109-014-1244-0 | ||
| 245 | 0 | 0 | |a Skeletal muscle proteomic signature and metabolic impairment in pulmonary hypertension |h [Elektronische Daten] |c [Simon Malenfant, François Potus, Frédéric Fournier, Sandra Breuils-Bonnet, Aude Pflieger, Sylvie Bourassa, Ève Tremblay, Benjamin Nehmé, Arnaud Droit, Sébastien Bonnet, Steeve Provencher] |
| 520 | 3 | |a Exercise limitation comes from a close interaction between cardiovascular and skeletal muscle impairments. To better understand the implication of possible peripheral oxidative metabolism dysfunction, we studied the proteomic signature of skeletal muscle in pulmonary arterial hypertension (PAH). Eight idiopathic PAH patients and eight matched healthy sedentary subjects were evaluated for exercise capacity, skeletal muscle proteomic profile, metabolism, and mitochondrial function. Skeletal muscle proteins were extracted, and fractioned peptides were tagged using an iTRAQ protocol. Proteomic analyses have documented a total of 9 downregulated proteins in PAH skeletal muscles and 10 upregulated proteins compared to healthy subjects. Most of the downregulated proteins were related to mitochondrial structure and function. Focusing on skeletal muscle metabolism and mitochondrial health, PAH patients presented a decreased expression of oxidative enzymes (pyruvate dehydrogenase, p < 0.01) and an increased expression of glycolytic enzymes (lactate dehydrogenase activity, p < 0.05). These findings were supported by abnormal mitochondrial morphology on electronic microscopy, lower citrate synthase activity (p < 0.01) and lower expression of the transcription factor A of the mitochondria (p < 0.05), confirming a more glycolytic metabolism in PAH skeletal muscles. We provide evidences that impaired mitochondrial and metabolic functions found in the lungs and the right ventricle are also present in skeletal muscles of patients. Key message: • Proteomic and metabolic analysis show abnormal oxidative metabolism in PAH skeletal muscle. • EM of PAH patients reveals abnormal mitochondrial structure and distribution. • Abnormal mitochondrial health and function contribute to exercise impairments of PAH. • PAH may be considered a vascular affliction of heart and lungs with major impact on peripheral muscles. | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2014 | ||
| 690 | 7 | |a Pulmonary hypertension |2 nationallicence | |
| 690 | 7 | |a Skeletal muscle |2 nationallicence | |
| 690 | 7 | |a Mitochondrial metabolism |2 nationallicence | |
| 690 | 7 | |a Proteomic |2 nationallicence | |
| 690 | 7 | |a Exercise capacity |2 nationallicence | |
| 700 | 1 | |a Malenfant |D Simon |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | |
| 700 | 1 | |a Potus |D François |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | |
| 700 | 1 | |a Fournier |D Frédéric |u Proteomics Center and Department of Molecular Medicine, CHUQ Research Center, Laval University, Quebec, QC, Canada |4 aut | |
| 700 | 1 | |a Breuils-Bonnet |D Sandra |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | |
| 700 | 1 | |a Pflieger |D Aude |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | |
| 700 | 1 | |a Bourassa |D Sylvie |u Proteomics Center and Department of Molecular Medicine, CHUQ Research Center, Laval University, Quebec, QC, Canada |4 aut | |
| 700 | 1 | |a Tremblay |D Ève |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | |
| 700 | 1 | |a Nehmé |D Benjamin |u Proteomics Center and Department of Molecular Medicine, CHUQ Research Center, Laval University, Quebec, QC, Canada |4 aut | |
| 700 | 1 | |a Droit |D Arnaud |u Proteomics Center and Department of Molecular Medicine, CHUQ Research Center, Laval University, Quebec, QC, Canada |4 aut | |
| 700 | 1 | |a Bonnet |D Sébastien |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | |
| 700 | 1 | |a Provencher |D Steeve |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | |
| 773 | 0 | |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/5(2015-05-01), 573-584 |x 0946-2716 |q 93:5<573 |1 2015 |2 93 |o 109 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00109-014-1244-0 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00109-014-1244-0 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Malenfant |D Simon |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Potus |D François |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Fournier |D Frédéric |u Proteomics Center and Department of Molecular Medicine, CHUQ Research Center, Laval University, Quebec, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Breuils-Bonnet |D Sandra |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Pflieger |D Aude |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bourassa |D Sylvie |u Proteomics Center and Department of Molecular Medicine, CHUQ Research Center, Laval University, Quebec, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Tremblay |D Ève |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Nehmé |D Benjamin |u Proteomics Center and Department of Molecular Medicine, CHUQ Research Center, Laval University, Quebec, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Droit |D Arnaud |u Proteomics Center and Department of Molecular Medicine, CHUQ Research Center, Laval University, Quebec, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bonnet |D Sébastien |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Provencher |D Steeve |u Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Service de Pneumologie, 2725 Chemin Sainte-Foy, G1V 4G5, Québec City, QC, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/5(2015-05-01), 573-584 |x 0946-2716 |q 93:5<573 |1 2015 |2 93 |o 109 | ||