Document Detail


Formation of plexiform lesions in experimental severe pulmonary arterial hypertension.
MedLine Citation:
PMID:  20547927     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The plexiform lesion is the hallmark of severe pulmonary arterial hypertension. However, its genesis and hemodynamic effects are largely unknown because of the limited availability of lung tissue samples from patients with pulmonary arterial hypertension and the lack of appropriate animal models. This study investigated whether rats with severe progressive pulmonary hypertension developed plexiform lesions. METHODS AND RESULTS: After a single subcutaneous injection of the vascular endothelial growth factor receptor blocker Sugen 5416, rats were exposed to hypoxia for 3 weeks. They were then returned to normoxia for an additional 10 to 11 weeks. Hemodynamic and histological examinations were performed at 13 to 14 weeks after the Sugen 5416 injection. All rats developed pulmonary hypertension (right ventricular systolic pressure approximately 100 mm Hg) and severe pulmonary arteriopathy, including concentric neointimal and complex plexiform-like lesions. There were 2 patterns of complex lesion formation: a lesion forming within the vessel lumen (stalk-like) and another that projected outside the vessel (aneurysm-like). Immunohistochemical analyses showed that these structures had cellular and molecular features closely resembling human plexiform lesions. CONCLUSIONS: Severe, sustained pulmonary hypertension in a very late stage of the Sugen 5416/hypoxia/normoxia-exposed rat is accompanied by the formation of lesions that are indistinguishable from the pulmonary arteriopathy of human pulmonary arterial hypertension. This unique model provides a new and rigorous approach for investigating the genesis, hemodynamic effects, and reversibility of plexiform and other occlusive lesions in pulmonary arterial hypertension.
Authors:
Kohtaro Abe; Michie Toba; Abdallah Alzoubi; Masako Ito; Karen A Fagan; Carlyne D Cool; Norbert F Voelkel; Ivan F McMurtry; Masahiko Oka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-14
Journal Detail:
Title:  Circulation     Volume:  121     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-29     Completed Date:  2010-08-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2747-54     Citation Subset:  AIM; IM    
Affiliation:
Department of Pharmacology, Center for Lung Biology, University of South Alabama, AL, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia
Arteries / pathology
Disease Models, Animal*
Hypertension, Pulmonary / etiology,  pathology*
Lung / blood supply
Rats
Vascular Endothelial Growth Factor A / antagonists & inhibitors
Chemical
Reg. No./Substance:
0/Vascular Endothelial Growth Factor A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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