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Skeletal muscle mitochondrial dysfunction precedes right ventricular impairment in experimental pulmonary hypertension

Enache, Irina and Charles, Anne-Laure and Bouitbir, Jamal and Favret, Fabrice and Zoll, Joffrey and Metzger, Daniel and Oswald-Mammosser, Monique and Geny, Bernard and Charloux, Anne. (2013) Skeletal muscle mitochondrial dysfunction precedes right ventricular impairment in experimental pulmonary hypertension. Molecular and cellular biochemistry, 373 (1-2). pp. 161-170.

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Official URL: https://edoc.unibas.ch/78250/

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Abstract

We assessed the time courses of mitochondrial biogenesis factors and respiration in the right ventricle (RV), gastrocnemius (GAS), and left ventricle (LV) in a model of pulmonary-hypertensive rats. Monocrotaline (MT) rats and controls were studied 2 and 4 weeks after injection. Compensated and decompensated heart failure stages were defined according to obvious congestion signs. mRNA expression and protein level of peroxisome proliferator activated receptor gamma co-activator 1α (PGC-1α), citrate synthase (CS) mRNA and activity, and mitochondrial respiration were investigated. In addition, mRNA expression of sirtuin1, nuclear respiratory factor 1, and mitochondrial transcription factor A were studied. As early as 2 weeks, the expression of the studied genes was decreased in the MT GAS. At 4 weeks, the MT GAS and MT RV showed decreased mRNA levels whatever the stage of disease, but PGC-1α protein and CS activity were significantly reduced only at the decompensated stage. The functional result was a significant fall in mitochondrial respiration at the decompensated stage in the RV and GAS. The mRNA expression and mitochondrial respiration were not significantly modified in the MT LV. MT rats demonstrated an early decrease in expression of genes involved in mitochondrial biogenesis in a skeletal muscle, whereas reduced protein expression, and the resulting mitochondrial respiratory dysfunction appeared only in rats with overt heart failure, in the GAS and RV. Dissociations between mRNA and protein levels at the compensated stage deserve to be further studied.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften
UniBasel Contributors:Bouitbir, Jamal
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Springer
ISSN:0300-8177
e-ISSN:1573-4919
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:03 Nov 2020 16:29
Deposited On:03 Nov 2020 16:29

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