Basic fibroblast growth factor expression precedes flow-induced arterial enlargement.
Arteries enlarge in response to increased blood flow, but the molecular signals controlling this enlargement are not well understood. Basic fibroblast growth factor (bFGF) is a potent mitogen for endothelial cells (EC) and smooth muscle cells (SMC) and promotes cellular proliferation and differentiation. In order to determine whether bFGF is expressed in response to increased blood flow in vivo, carotid-jugular arteriovenous fistulas (AVF) were created in Japanese white rabbits. The carotid artery proximal to the fistula was harvested after 1, 3, or 7 days and compared to nonoperated, control carotid arteries. Arterial blood flow increased five- to eightfold in all AVF animals and resulted in a significant increase in wall shear stress. The proximal carotid artery arterial diameter was no different from control after 1 and 3 days (2.3 +/- 0. 1 mm) but enlarged to 2.9 +/- 0.1 mm (P < 0.05) after 7 days. RT-PCR revealed early transcription of bFGF mRNA at 1 and 3 days with increased densitometric band ratio (bFGF/beta-actin) at 7 days. Immunohistochemical analysis revealed bFGF protein localization in EC of control arteries as well as AVF arteries at all time points. SMC and adventitia expression of bFGF was absent in controls, minimal at 1 day, and increased after 3 and 7 days in the experimental groups. Western blotting confirmed the presence of bFGF in samples and transmission immunoelectron microscopy confirmed its nuclear localization. Endothelial cells in vivo express bFGF under both normal and elevated flow conditions. Smooth muscle cells, however, do not express bFGF under normal flow conditions but begin to express bFGF after 1 day of high flow with increased expression after 3 and 7 days. Flow-induced arterial enlargement begins after SMC expression of bFGF. Therefore, bFGF may play a role in arterial enlargement and adaptive remodeling in response to increased flow.
Singh
T M
TM
Department of Vascular Surgery, Stanford University, Stanford, California, 94305, USA.
Abe
K Y
KY
Sasaki
T
T
Zhuang
Y J
YJ
Masuda
H
H
Zarins
C K
CK
D000714:Anastomosis, Surgical; D000818:Animals; D000906:Antibodies; D015153:Blotting, Western; D017536:Carotid Artery, Common / Q000502:physiology* / Q000601:surgery; D004730:Endothelium, Vascular / Q000737:chemistry / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D015870:Gene Expression / Q000502:physiology; D007150:Immunohistochemistry; D007601:Jugular Veins / Q000502:physiology* / Q000601:surgery; D016133:Polymerase Chain Reaction; D011817:Rabbits; D012039:Regional Blood Flow / Q000502:physiology; D013314:Stress, Mechanical; D013961:Thyroid Gland / Q000098:blood supply
D000906:Antibodies; D016222:Fibroblast Growth Factor 2