Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Seimetz, M; Parajuli, N; Pichl, A; Veit, F; Kwapiszewska, G; Weisel, FC; Milger, K; Egemnazarov, B; Turowska, A; Fuchs, B; Nikam, S; Roth, M; Sydykov, A; Medebach, T; Klepetko, W; Jaksch, P; Dumitrascu, R; Garn, H; Voswinckel, R; Kostin, S; Seeger, W; Schermuly, RT; Grimminger, F; Ghofrani, HA; Weissmann, N.
Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice.
Cell. 2011; 147(2): 293-305.
Doi: 10.1016/j.cell.2011.08.035
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- Co-Autor*innen der Med Uni Graz
- Egemnazarov Bakytbek
- Kwapiszewska-Marsh Grazyna
- Milger-Kneidinger Katrin
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- Abstract:
- Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death worldwide. We report in an emphysema model of mice chronically exposed to tobacco smoke that pulmonary vascular dysfunction, vascular remodeling, and pulmonary hypertension (PH) precede development of alveolar destruction. We provide evidence for a causative role of inducible nitric oxide synthase (iNOS) and peroxynitrite in this context. Mice lacking iNOS were protected against emphysema and PH. Treatment of wild-type mice with the iNOS inhibitor N(6)-(1-iminoethyl)-L-lysine (L-NIL) prevented structural and functional alterations of both the lung vasculature and alveoli and also reversed established disease. In chimeric mice lacking iNOS in bone marrow (BM)-derived cells, PH was dependent on iNOS from BM-derived cells, whereas emphysema development was dependent on iNOS from non-BM-derived cells. Similar regulatory and structural alterations as seen in mouse lungs were found in lung tissue from humans with end-stage COPD. Copyright © 2011 Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Disease Models, Animal -
- Humans -
- Hypertension, Pulmonary - chemically induced Hypertension, Pulmonary - drug therapy Hypertension, Pulmonary - pathology Hypertension, Pulmonary - physiopathology
- Lung - blood supply Lung - pathology Lung - physiopathology
- Lysine - analogs and derivatives Lysine - pharmacology
- Male -
- Mice -
- Mice, Inbred C57BL -
- Nitric Oxide Synthase Type II - antagonists and inhibitors Nitric Oxide Synthase Type II - genetics
- Pulmonary Alveoli - pathology Pulmonary Alveoli - physiopathology
- Pulmonary Disease, Chronic Obstructive - chemically induced Pulmonary Disease, Chronic Obstructive - drug therapy Pulmonary Disease, Chronic Obstructive - pathology Pulmonary Disease, Chronic Obstructive - physiopathology
- Pulmonary Emphysema - chemically induced Pulmonary Emphysema - drug therapy Pulmonary Emphysema - pathology Pulmonary Emphysema - physiopathology
- Smoking - pathology