© 1999 American Heart Association, Inc.
Original Contribution |
Vascular Remodeling in Response to Altered Blood Flow Is Mediated by Fibroblast Growth Factor-2
From the Center for Molecular Medicine (S.R.B., V.L.), Maine Medical Center Research Institute, South Portland, Maine; Texas Biotechnology Corporation (R.J.B., D.A.E., A.R.), Houston, Tex.
Correspondence to Volkhard Lindner, MD, PhD, Center for Molecular Medicine, Maine Medical Center Research Institute, 125 John Roberts Rd, Suite 12, South Portland, ME 04106. E-mail lindnv{at}poa.mmc.org
Abstract—Vascular structures adapt to changes in blood flow by adjusting their diameter accordingly. The factors mediating this process are only beginning to be identified. We have recently established a mouse model of arterial remodeling in which flow in the common carotid artery is interrupted by ligation of the vessel near the carotid bifurcation, resulting in a dramatic reduction in vessel diameter as a consequence of inward remodeling and intimal lesion formation. In the present study, we used this model to determine the role of fibroblast growth factor-2 (FGF-2) in the remodeling response by maintaining neutralizing serum levels of a mouse monoclonal antibody against FGF-2 for 4 weeks. Morphometric analysis revealed that intimal lesion formation was not affected by the antibody. However, lumen narrowing was significantly inhibited, resulting in a greater than 3-fold increase in lumen area in anti–FGF-2–treated animals compared with controls. Treatment with anti–FGF-2 antibody significantly inhibited the reduction in vessel diameter (inward remodeling) and shortening of the internal elastic lamina in the ligated vessel. In addition, anti–FGF-2 treatment also caused outward remodeling of the contralateral carotid artery. These findings identify FGF-2 as an important factor in vascular remodeling, and its effects are likely to be mediated by increasing vascular tone. The results are consistent with the recent observation of reduced vascular tone in the FGF-2–deficient mouse.
Key Words: basic fibroblast growth factor • fibroblast growth factor-2 • intima • smooth muscle
This article has been cited by other articles:
 |
|
 |
|
  J. A.I. Virag, M. L. Rolle, J. Reece, S. Hardouin, E. O. Feigl, and C. E. Murry Fibroblast Growth Factor-2 Regulates Myocardial Infarct Repair: Effects on Cell Proliferation, Scar Contraction, and Ventricular Function Am. J. Pathol., November 1, 2007; 171(5): 1431 - 1440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liao, C. P. Regan, I. Manabe, G. K. Owens, K. H. Day, D. N. Damon, and B. R. Duling Smooth Muscle-Targeted Knockout of Connexin43 Enhances Neointimal Formation in Response to Vascular Injury Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1037 - 1042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Raj, P. Kanellakis, G. Pomilio, G. Jennings, A. Bobik, and A. Agrotis Inhibition of Fibroblast Growth Factor Receptor Signaling Attenuates Atherosclerosis in Apolipoprotein E-Deficient Mice Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1845 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Sen, S. Khanna, and S. Roy Perceived hyperoxia: Oxygen-induced remodeling of the reoxygenated heart Cardiovasc Res, July 15, 2006; 71(2): 280 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pyagay, M. Heroult, Q. Wang, W. Lehnert, J. Belden, L. Liaw, R. E. Friesel, and V. Lindner Collagen Triple Helix Repeat Containing 1, a Novel Secreted Protein in Injured and Diseased Arteries, Inhibits Collagen Expression and Promotes Cell Migration Circ. Res., February 4, 2005; 96(2): 261 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Lindner, Q. Wang, B. A. Conley, R. E. Friesel, and C. P.H. Vary Vascular Injury Induces Expression of Periostin: Implications for Vascular Cell Differentiation and Migration Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 77 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Kerlin, B. C. Cooley, B. H. Isermann, I. Hernandez, R. Sood, M. Zogg, S. B. Hendrickson, M. W. Mosesson, S. Lord, and H. Weiler Cause-effect relation between hyperfibrinogenemia and vascular disease Blood, March 1, 2004; 103(5): 1728 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kuzuya, S. Kanda, T. Sasaki, N. Tamaya-Mori, X. W. Cheng, T. Itoh, S. Itohara, and A. Iguchi Deficiency of Gelatinase A Suppresses Smooth Muscle Cell Invasion and Development of Experimental Intimal Hyperplasia Circulation, September 16, 2003; 108(11): 1375 - 1381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Myers, K. J. Harmon, V. Lindner, and L. Liaw Alterations of Arterial Physiology in Osteopontin-Null Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2003; 23(6): 1021 - 1028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Detillieux, F. Sheikh, E. Kardami, and P. A. Cattini Biological activities of fibroblast growth factor-2 in the adult myocardium Cardiovasc Res, January 1, 2003; 57(1): 8 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Kranenburg, W. I. de Boer, J. H. J.M. van Krieken, W. J. Mooi, J. E. Walters, P. R. Saxena, P. J. Sterk, and H. S. Sharma Enhanced Expression of Fibroblast Growth Factors and Receptor FGFR-1 during Vascular Remodeling in Chronic Obstructive Pulmonary Disease Am. J. Respir. Cell Mol. Biol., November 1, 2002; 27(5): 517 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shi, G. Perry, M. S. Berridge, G. Aliev, S. L. Siedlak, M. A. Smith, J. C. LaManna, and R. P. Friedland Labeling of Cerebral Amyloid {beta} Deposits In Vivo Using Intranasal Basic Fibroblast Growth Factor and Serum Amyloid P Component in Mice J. Nucl. Med., August 1, 2002; 43(8): 1044 - 1051. [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]
|
|
|
|
|
|
B. S. Buetow, J. R. Crosby, W. E. Kaminski, R. K. Ramachandran, P. Lindahl, P. Martin, C. Betsholtz, R. A. Seifert, E. W. Raines, and D. F. Bowen-Pope Platelet-Derived Growth Factor B-Chain of Hematopoietic Origin Is Not Necessary for Granulation Tissue Formation and Its Absence Enhances Vascularization Am. J. Pathol., November 1, 2001; 159(5): 1869 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Weiler, V. Lindner, B. Kerlin, B. H. Isermann, S. B. Hendrickson, B. C. Cooley, D. A. Meh, M. W. Mosesson, N. W. Shworak, M. J. Post, et al. Characterization of a Mouse Model for Thrombomodulin Deficiency Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1531 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. McPherson, K. G. Barringhaus, G. G. Bishop, J. M. Sanders, J. M. Rieger, S. E. Hesselbacher, L. W. Gimple, E. R. Powers, T. Macdonald, G. Sullivan, et al. Adenosine A2A Receptor Stimulation Reduces Inflammation and Neointimal Growth in a Murine Carotid Ligation Model Arterioscler. Thromb. Vasc. Biol., May 1, 2001; 21(5): 791 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Godin, E. Ivan, C. Johnson, R. Magid, and Z. S. Galis Remodeling of Carotid Artery Is Associated With Increased Expression of Matrix Metalloproteinases in Mouse Blood Flow Cessation Model Circulation, December 5, 2000; 102(23): 2861 - 2866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. N. T. P. Bakker, E. T. van der Meulen, J. A. E. Spaan, and E. VanBavel Organoid culture of cannulated rat resistance arteries: effect of serum factors on vasoactivity and remodeling Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1233 - H1240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. MAYR, C. LI, Y. ZOU, U. HUEMER, Y. HU, and Q. XU Biomechanical stress-induced apoptosis in vein grafts involves p38 mitogen-activated protein kinases FASEB J, February 1, 2000; 14(2): 261 - 270. [Abstract] [Full Text]
|
|
|
|
|
|
R. Singh, S. Pan, C. S. Mueske, T. Witt, L. S. Kleppe, T. E. Peterson, A. Slobodova, J.-Y. Chang, N. M. Caplice, and R. D. Simari Role for Tissue Factor Pathway in Murine Model of Vascular Remodeling Circ. Res., July 6, 2001; 89(1): 71 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Buus, F. Pourageaud, G. E. Fazzi, G. Janssen, M. J. Mulvany, and J. G.R. De Mey Smooth Muscle Cell Changes During Flow-Related Remodeling of Rat Mesenteric Resistance Arteries Circ. Res., July 20, 2001; 89(2): 180 - 186. [Abstract] [Full Text] [PDF]
|
|