© 1997 American Heart Association, Inc.
Articles |
Platelet-Derived Growth Factor Ligand and Receptor Expression in Response to Altered Blood Flow In Vivo
From the Department of Surgery (J.S.M., R.H.D., R.L.G.), The Bowman Gray School of Medicine, Winston-Salem, NC; the Maine Medical Center Research Institute (V.L.), Portland; and the University of Washington School of Medicine (J.K.M., B.C.B.), Seattle.
Correspondence to Randolph L. Geary, MD, Division of Surgical Sciences, The Bowman Gray School of Medicine, Wake Forest University, Medical Center Blvd, Winston-Salem, NC 27157. E-mail rgeary{at}bgsm.edu
Abstract Blood flow and the tractive force shear stress are
important determinants of artery caliber, and reduced shear predisposes
arteries to intimal thickening and atherosclerosis. The
molecular basis for shear-induced changes in artery wall structure is
poorly defined. A number of factors associated with normal and
pathological artery wall remodeling are induced by shear stress in
endothelial cell cultures. These include
platelet-derived growth factor (PDGF), a potent mitogen,
chemoattractant, and vasoconstrictor. To determine whether similar
changes occur in vivo, we examined the effects of reduced blood flow on
endothelial cell PDGF expression and proliferation in
the rat carotid artery. Branches of the right internal and external
carotid arteries were ligated, reducing common carotid artery blood
flow from 8.0±0.6 to 0.5±0.1 mL/min while increasing flow in the left
carotid from 7.1±0.6 to 10.8±0.7 mL/min. Shear stress following the
procedure was 1.4±0.2 and 33.4±1.1 dyne/cm2 in carotids
with reduced blood flow (RF) and increased blood flow (IF),
respectively. Arteries were harvested 6, 24, 48, or 72 hours after
ligation, perfusion-fixed, and opened longitudinally.
Endothelial cell proliferation (bromodeoxyuridine
[BrdU] labeling) was assessed en face at 24, 48, and 72 hours;
expression of mRNA for PDGF-A and -B chains and PDGF 
- and
ß-receptors (in situ hybridization) was determined at 6, 48, and 72
hours after unilateral flow reduction. RF induced
endothelial cell proliferation, which peaked at 48
hours (RF BrdU labeling: 24 hours, 0.4±0.2%; 48 hours, 7.2±2.0%;
and 72 hours, 4.1±0.6%; n=5). PDGF-B expression increased in RF
compared with IF endothelium within 48 hours and
persisted at 72 hours (percent labeling [RF/IFx100]: 6 hours,
76±20%; 48 hours, 395±179%; and 72 hours, 208±44%; n=3). PDGF-A
expression was similarly increased in RF endothelium.
In contrast, expression of PDGF - and ß-receptors was undetectable
in RF and IF endothelium at all times. We conclude that
endothelial cell PDGF ligand expression is induced by
reduced shear stress in vivo and may play an important role in
flow-mediated remodeling and atherogenesis.
Key Words: endothelial cell • shear stress • blood flow • platelet-derived growth factor • proliferation
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