Document Detail


Fibroblast growth factor-2 expression is altered in lambs with increased pulmonary blood flow and pulmonary hypertension.
MedLine Citation:
PMID:  17211137     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A lamb model of pulmonary hypertension, developed by inserting an aortopulmonary vascular graft (shunt), displays vascular remodeling and increased pulmonary blood flow characteristic of children with congenital heart disease. The purpose of this study was to determine whether expression of fibroblast growth factor-2 (FGF-2), a smooth muscle cell mitogen, is altered in shunt lambs. FGF-2 mRNA and protein levels were increased in lung tissue extracts from shunt lambs at 4 wk of age relative to age-matched controls (p < 0.05). FGF-2 protein levels were also increased in the pulmonary arteries and serum of shunt lambs (p < 0.05). Pulmonary arterial smooth muscle cells (PASMC) and endothelial cells (PAEC) were isolated from 4 wk-old lambs and subjected to cyclic stretch and laminar shear stress to mimic increased pulmonary blood flow. Stretch and shear increased FGF-2 promoter activity, and intracellular and extracellular FGF-2 protein levels in both cell types (p < 0.05). Exogenous FGF-2 stimulated PASMC proliferation at levels detected in the extracellular medium of sheared cells (p < 0.05). Elevated FGF-2 signaling by PASMC and PAEC exposed to increased pulmonary blood flow may play a role in the pulmonary vascular remodeling associated with the shunt model of pulmonary hypertension secondary to congenital heart disease.
Authors:
Stephen Wedgwood; Jennifer M Devol; Albert Grobe; Eileen Benavidez; Anthony Azakie; Jeffrey R Fineman; Stephen M Black
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatric research     Volume:  61     ISSN:  0031-3998     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-09     Completed Date:  2007-02-07     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32-6     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Northwestern University, Chicago, Illinois 60611, USA. s-wedgwood@northwestern.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Fibroblast Growth Factor 2 / biosynthesis,  genetics*
Hypertension, Pulmonary / metabolism*
Lung / blood supply*
RNA, Messenger / metabolism
Regional Blood Flow
Sheep
Signal Transduction / physiology
Grant Support
ID/Acronym/Agency:
HL070061/HL/NHLBI NIH HHS; HL072123/HL/NHLBI NIH HHS; HL60190/HL/NHLBI NIH HHS; HL61284/HL/NHLBI NIH HHS; HL67841/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 103107-01-3/Fibroblast Growth Factor 2

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


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