| Extracellular superoxide dismutase overexpression can reverse the course of hypoxia-induced pulmonary hypertension. | |
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MedLine Citation:
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PMID: 22045221 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hypoxia leads to free radical production, which has a pivotal role in the pathophysiology of pulmonary hypertension (PH). We hypothesized that treatment with extracellular superoxide dismutase (EC-SOD) could ameliorate the development of PH induced by hypoxia. In vitro studies using pulmonary microvascular endothelial cells showed that cells transfected with EC-SOD had significantly less accumulation of xanthine oxidase and reactive oxygen species than nontransfected cells after hypoxia exposure for 24 h. To study the prophylactic role of EC-SOD, adult male wild-type (WT) and transgenic (TG) mice, with lung-specific overexpression of human EC-SOD (hEC-SOD), were exposed to fraction of inspired oxygen (FiO(2)) 10% for 10 d. After exposure, right ventricular systolic pressure (RVSP), right ventricular mass (RV/S + LV), pulmonary vascular wall thickness (PVWT) and pulmonary artery contraction/relaxation were assessed. TG mice were protected against PH compared with WT mice with significantly lower RVSP (23.9 ± 1.24 versus 47.2 ± 3.4), RV/S + LV (0.287 ± 0.015 versus 0.335 ± 0.022) and vascular remodeling, indicated by PVWT (14.324 ± 1.107 versus 18.885 ± 1.529). Functional studies using pulmonary arteries isolated from mice indicated that EC-SOD prevents hypoxia-mediated attenuation of nitric oxide-induced relaxation. Therapeutic potential was assessed by exposing WT mice to FiO(2) 10% for 10 d. Half of the group was transfected with plasmid containing cDNA encoding human EC-SOD. The remaining animals were transfected with empty vector. Both groups were exposed to FiO(2) 10% for a further 10 d. Transfected mice had significantly reduced RVSP (18.97 ± 1.12 versus 41.3 ± 1.5), RV/S + LV (0.293 ± 0.012 versus 0.372 ± 0.014) and PVWT (12.51 ± 0.72 versus 18.98 ± 1.24). On the basis of these findings, we concluded that overexpression of EC-SOD prevents the development of PH and ameliorates established PH. |
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Authors:
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Mohamed N Ahmed; Yinzhong Zhang; Champa Codipilly; Nahla Zaghloul; Dhara Patel; Michael Wolin; Edmund J Miller |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-02-10 |
Journal Detail:
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Title: Molecular medicine (Cambridge, Mass.) Volume: 18 ISSN: 1528-3658 ISO Abbreviation: Mol. Med. Publication Date: 2012 |
Date Detail:
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Created Date: 2012-02-13 Completed Date: 2012-06-01 Revised Date: 2013-05-23 |
Medline Journal Info:
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Nlm Unique ID: 9501023 Medline TA: Mol Med Country: United States |
Other Details:
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Languages: eng Pagination: 38-46 Citation Subset: IM |
Affiliation:
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Cohen Children's Medical Center, North Shore-Long Island Jewish Health System, New Hyde Park, New York, United States of America. mahmed2@nshs.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anoxia / physiopathology* Cells, Cultured DNA, Complementary / genetics Humans Hypertension, Pulmonary / etiology*, therapy* Male Mice Mice, Transgenic Superoxide Dismutase / genetics, metabolism* Transfection Xanthine Oxidase / metabolism |
| Chemical | |
Reg. No./Substance:
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0/DNA, Complementary; EC 1.15.1.1/Superoxide Dismutase; EC 1.17.3.2/Xanthine Oxidase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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