Fibroblast growth factor-2 expression is altered in lambs with increased pulmonary blood flow and pulmonary hypertension

Stephen Wedgwood, Jennifer M. Devol, Albert Grobe, Eileen Benavidez, Anthony Azakie, Jeffrey R. Fineman, Stephen Matthew Black

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)32-36
Number of pages5
JournalPediatric Research
Volume61
Issue number1
DOIs
StatePublished - Jan 1 2007

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Fibroblast Growth Factor 2
Pulmonary Hypertension
Lung
Smooth Muscle Myocytes
Heart Diseases
Endothelial Cells
Proteins
Tissue Extracts
Mitogens
Pulmonary Artery
Blood Vessels
Cell Proliferation
Transplants
Messenger RNA
Serum

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Fibroblast growth factor-2 expression is altered in lambs with increased pulmonary blood flow and pulmonary hypertension. / Wedgwood, Stephen; Devol, Jennifer M.; Grobe, Albert; Benavidez, Eileen; Azakie, Anthony; Fineman, Jeffrey R.; Black, Stephen Matthew.

In: Pediatric Research, Vol. 61, No. 1, 01.01.2007, p. 32-36.

Research output: Contribution to journalArticle

Wedgwood, Stephen ; Devol, Jennifer M. ; Grobe, Albert ; Benavidez, Eileen ; Azakie, Anthony ; Fineman, Jeffrey R. ; Black, Stephen Matthew. / Fibroblast growth factor-2 expression is altered in lambs with increased pulmonary blood flow and pulmonary hypertension. In: Pediatric Research. 2007 ; Vol. 61, No. 1. pp. 32-36.
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