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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Mitochondrial hyperpolarization in pulmonary vascular remodeling: Mitochondrial uncoupling protein deficiency as disease model
American Journal of Respiratory Cell and Molecular Biology, Volume 49, No. 3, Year 2013
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Description
Alterations of mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial respiration are possible triggers of pulmonary vascular remodeling in pulmonary hypertension (PH). We investigated the role of MMP in PH and hypothesized that deletion of the mitochondrial uncoupling protein 2 (UCP2) increases MMP, thus promoting pulmonary vascular remodeling and PH. MMP was measured by JC-1 in isolated pulmonary arterial smooth muscle cells (PASMCs) of patients with PH and animals with PHinducedby exposure tomonocrotaline(MCT)or chronic hypoxia. PH was quantified in vivo in UCP2-deficient (UCP2-/-) mice by hemodynamics, morphometry, and echocardiography. ROS were measured by electron spin resonance spectroscopy and proliferation by thymidine incorporation. Mitochondrial respiration was investigated by high-resolution respirometry. MMP was increased in PASMCs of patients and in animal models of PH. UCP2-/- mice exhibited pulmonary vascular remodeling and mild PH compared with wild-type (WT) mice. PASMCs of UCP2-/- mice showed increased proliferation, MMP, and ROS release. Increased proliferation of UCP2-/- PASMCs could be attenuated by ROS inhibitors and inhibited by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone, which decreased MMP to the level of WT mice. Mitochondrial respiration was altered in PASMCs from MCT rats and PASMCs exposed to hypoxia but not in isolated pulmonary mitochondria of UCP2-/- mice orPASMCs after treatment with small interfering RNA for UCP2. Our data suggest that increased MMP causes vascular remodeling in UCP2-/- mice partially via increased ROS. In chronic hypoxia and MCT-induced PH, additional pathomechanisms such as decreased respiration may play a role. Copyright © 2013 by the American Thoracic Society.
Authors & Co-Authors
Pak, Oleg A.
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Sommer, Natascha
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Bakr, Adel G.
Egypt, Cairo
Faculty of Pharmacy
Waisbrod, Sharon
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Sydykov, Akylbek
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Haag, Daniela
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Esfandiary, Azadeh
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Kojonazarov, Baktybek
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Veit, Florian
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Fuchs, Beate
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Weisel, Friederike Christine
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Hecker, Matthias
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Schermuly, Ralph Theo
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Grimminger, Friedrich
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Ghofrani, Hossein Ardeschir
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Seeger, Werner
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Weißmann, Norbert
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Statistics
Citations: 65
Authors: 17
Affiliations: 2
Identifiers
Doi:
10.1165/rcmb.2012-0361OC
ISSN:
10441549
e-ISSN:
15354989
Research Areas
Noncommunicable Diseases