© 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
This article has been cited by other articles:
 |
|
 |
|
  A Valentin, L Cardamone, S Baek, and J.D Humphrey Complementary vasoactivity and matrix remodelling in arterial adaptations to altered flow and pressure J R Soc Interface, March 6, 2009; 6(32): 293 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Andrae, R. Gallini, and C. Betsholtz Role of platelet-derived growth factors in physiology and medicine Genes & Dev., May 15, 2008; 22(10): 1276 - 1312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. E. Hastings, M. B. Simmers, O. G. McDonald, B. R. Wamhoff, and B. R. Blackman Atherosclerosis-prone hemodynamics differentially regulates endothelial and smooth muscle cell phenotypes and promotes pro-inflammatory priming Am J Physiol Cell Physiol, December 1, 2007; 293(6): C1824 - C1833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Bonello, Y. V. Bobryshev, and L. M. Khachigian Peroxide-Inducible Ets-1 Mediates Platelet-Derived Growth Factor Receptor-{alpha} Gene Transcription in Vascular Smooth Muscle Cells Am. J. Pathol., October 1, 2005; 167(4): 1149 - 1159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Raymond, F. Guilbert, A. Metcalfe, G. Gevry, I. Salazkin, and O. Robledo Role of the Endothelial Lining in Recurrences After Coil Embolization: Prevention of Recanalization by Endothelial Denudation Stroke, June 1, 2004; 35(6): 1471 - 1475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Q. Liu, D. Tang, C. Tieche, and P. K. Alkema Pattern formation of vascular smooth muscle cells subject to nonuniform fluid shear stress: mediation by gradient of cell density Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1072 - H1080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Q. Liu, C. Tieche, D. Tang, and P. Alkema Pattern formation of vascular smooth muscle cells subject to nonuniform fluid shear stress: role of PDGF-{beta} receptor and Src Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1081 - H1090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ibrahim, J. K. Miyashiro, and B. C. Berk Shear Stress Is Differentially Regulated Among Inbred Rat Strains Circ. Res., May 16, 2003; 92(9): 1001 - 1009. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Balasubramaniam, T. D. Le Cras, D. D. Ivy, T. R. Grover, J. P. Kinsella, and S. H. Abman Role of platelet-derived growth factor in vascular remodeling during pulmonary hypertension in the ovine fetus Am J Physiol Lung Cell Mol Physiol, May 1, 2003; 284(5): L826 - L833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hong, S. Aksenov, X. Guan, J. T. Fallon, D. Waters, and C. Chen Remodeling of Small Intramyocardial Coronary Arteries Distal to a Severe Epicardial Coronary Artery Stenosis Arterioscler Thromb Vasc Biol, December 1, 2002; 22(12): 2059 - 2065. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Jussila and K. Alitalo Vascular Growth Factors and Lymphangiogenesis Physiol Rev, July 1, 2002; 82(3): 673 - 700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Sullivan and J. B. Hoying Flow-Dependent Remodeling in the Carotid Artery of Fibroblast Growth Factor-2 Knockout Mice Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1100 - 1105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Palumbo, C. Gaetano, A. Antonini, G. Pompilio, E. Bracco, L. Ronnstrand, C.-H. Heldin, and M. C. Capogrossi Different Effects of High and Low Shear Stress on Platelet-Derived Growth Factor Isoform Release by Endothelial Cells: Consequences for Smooth Muscle Cell Migration Arterioscler Thromb Vasc Biol, March 1, 2002; 22(3): 405 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Tuttle, R. D. Nachreiner, A. S. Bhuller, K. W. Condict, B. A. Connors, B. P. Herring, M. C. Dalsing, and J. L. Unthank Shear level influences resistance artery remodeling: wall dimensions, cell density, and eNOS expression Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1380 - H1389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Berk Vascular Smooth Muscle Growth: Autocrine Growth Mechanisms Physiol Rev, July 1, 2001; 81(3): 999 - 1030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Ward, G. Pasterkamp, A. C. Yeung, and C. Borst Arterial Remodeling : Mechanisms and Clinical Implications Circulation, September 5, 2000; 102(10): 1186 - 1191. [Full Text] [PDF]
|
|
|
|
|
|
R. Palumbo, C. Gaetano, G. Melillo, E. Toschi, A. Remuzzi, and M. C. Capogrossi Shear Stress Downregulation of Platelet-Derived Growth Factor Receptor-{beta} and Matrix Metalloprotease-2 Is Associated With Inhibition of Smooth Muscle Cell Invasion and Migration Circulation, July 11, 2000; 102(2): 225 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Harmon, L. L. Couper, and V. Lindner Strain-Dependent Vascular Remodeling Phenotypes in Inbred Mice Am. J. Pathol., May 1, 2000; 156(5): 1741 - 1748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Davies, E. L. Owens, D. P. Mason, H. Lea, P. K. Tran, S. Vergel, S. A. Hawkins, C. E. Hart, and A. W. Clowes Effect of Platelet-Derived Growth Factor Receptor-{alpha} and -{beta} Blockade on Flow-Induced Neointimal Formation in Endothelialized Baboon Vascular Grafts Circ. Res., April 14, 2000; 86(7): 779 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Pasterkamp, D. P.V de Kleijn, and C. Borst Arterial remodeling in atherosclerosis, restenosis and after alteration of blood flow: potential mechanisms and clinical implications Cardiovasc Res, March 1, 2000; 45(4): 843 - 852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fukuhara, R. L. Geary, D. I. Diz, P. E. Gallagher, J. A. Wilson, S. S. Glazier, R. H Dean, and C. M. Ferrario Angiotensin-Converting Enzyme Expression in Human Carotid Artery Atherosclerosis Hypertension, January 1, 2000; 35(1): 353 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Malek, S. L. Alper, and S. Izumo Hemodynamic Shear Stress and Its Role in Atherosclerosis JAMA, December 1, 1999; 282(21): 2035 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Q. Liu Focal Expression of Angiotensin II Type 1 Receptor and Smooth Muscle Cell Proliferation in the Neointima of Experimental Vein Grafts : Relation to Eddy Blood Flow Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2630 - 2639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Heldin and B. Westermark Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor Physiol Rev, October 1, 1999; 79(4): 1283 - 1316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Bryant, R. J. Bjercke, D. A. Erichsen, A. Rege, and V. Lindner Vascular Remodeling in Response to Altered Blood Flow Is Mediated by Fibroblast Growth Factor-2 Circ. Res., February 19, 1999; 84(3): 323 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ross Atherosclerosis -- An Inflammatory Disease N. Engl. J. Med., January 14, 1999; 340(2): 115 - 126. [Full Text] [PDF]
|
|
|
|
|
|
R. C. Ziegelstein, P. S. Blank, L. Cheng, and M. C. Capogrossi Cytosolic Alkalinization of Vascular Endothelial Cells Produced by an Abrupt Reduction in Fluid Shear Stress Circ. Res., April 20, 1998; 82(7): 803 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Miyashiro, V. Poppa, and B. C. Berk Flow-Induced Vascular Remodeling in the Rat Carotid Artery Diminishes With Age Circ. Res., September 19, 1997; 81(3): 311 - 319. [Abstract] [Full Text]
|
|