Document Detail


Gene expression patterns in the lungs of patients with primary pulmonary hypertension: a gene microarray analysis.
MedLine Citation:
PMID:  11282888     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Primary pulmonary hypertension (PPH) is a disease of unknown etiology characterized by lumen-obliterating endothelial cell proliferation and vascular smooth muscle hypertrophy of the small precapillary pulmonary arteries. Because the vascular lesions are homogeneously distributed throughout the entire lung, we propose that a tissue fragment of the lung is representative of the whole lung. RNA extracted from the fragments is likely to provide meaningful information regarding the changes in gene expression pattern in PPH when compared with structurally normal lung tissue. We hypothesize that the lung tissue gene expression pattern of patients with PPH has a characteristic profile when compared with the gene expression pattern of structurally normal lungs and that this characteristic gene expression profile provides new insights into the pathobiology of PPH. Using oligonucleotide microarray technology, we characterized the expression pattern in the lung tissue obtained from 6 patients with primary pulmonary hypertension (PPH)-including 2 patients with the familial form of PPH (FPPH)-and from 6 patients with histologically normal lungs. For the data analysis, gene clusters were generated and the gene expression pattern differences between PPH and normal lung tissue and between PPH and FPPH lung tissue were compared. All PPH lung tissue samples showed a decreased expression of genes encoding several kinases and phosphatases, whereas several oncogenes and genes coding for ion channel proteins were upregulated in their expression. Importantly, we could distinguish by pattern comparison between sporadic PPH and FPPH, because alterations in the expression of transforming growth factor-beta receptor III, bone morphogenic protein 2, mitogen-activated protein kinase kinase 5, RACK 1, apolipoprotein C-III, and the gene encoding the laminin receptor 1 were only found in the samples from patients with sporadic PPH, but not in FPPH samples. We conclude that the microarray gene expression technique is a new and useful molecular tool that provides novel information pertinent to a better characterization and understanding of the pathobiology of the distinct clinical phenotypes of pulmonary hypertension.
Authors:
M W Geraci; M Moore; T Gesell; M E Yeager; L Alger; H Golpon; B Gao; J E Loyd; R M Tuder; N F Voelkel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  88     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-04-03     Completed Date:  2001-05-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  555-62     Citation Subset:  IM    
Affiliation:
Division of Pulmonary Sciences and Critical Care Medicine, Pulmonary Hypertension Center, Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Female
Gene Expression Profiling*
Humans
Hypertension, Pulmonary / genetics*
Lung / metabolism*,  pathology
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
RNA / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
HL60913-01/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
63231-63-0/RNA

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


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