Fibroblast growth factor-2 expression is altered in lambs with increased pulmonary blood flow and pulmonary hypertension.
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.
Wedgwood
Stephen
S
Department of Pediatrics, Northwestern University, Chicago, Illinois 60611, USA. s-wedgwood@northwestern.edu
Devol
Jennifer M
JM
Grobe
Albert
A
Benavidez
Eileen
E
Azakie
Anthony
A
Fineman
Jeffrey R
JR
Black
Stephen M
SM
D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics*; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D008168:Lung / Q000098:blood supply*; D012333:RNA, Messenger / Q000378:metabolism; D012039:Regional Blood Flow; D012756:Sheep; D015398:Signal Transduction / Q000502:physiology
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2