Circulation Research, Vol 68, 106-113, Copyright © 1991 by American Heart Association

ARTICLES

Role of basic fibroblast growth factor in vascular lesion formation

V Lindner, DA Lappi, A Baird, RA Majack and MA Reidy
Department of Pathology, School of Medicine, University of Washington, Seattle 98195.

In the present study we investigated whether basic fibroblast growth factor (bFGF) plays a role in the proliferative response of smooth muscle cells (SMCs) to denuding injury. Rat carotid smooth muscle was found to express the mRNA for bFGF, and bFGF protein was found to be present in rat aorta by immunoblot analysis. Systemically administered bFGF was a potent mitogen for vascular SMCs in arteries denuded with a balloon catheter, increasing replication from 11.5% in controls to 54.8%. Denudation with a device (filament loop), which causes only minimal damage to medial SMCs, showed a similar increase in replication (1.3% versus 43.3%) after bFGF infusion. In unmanipulated vessels, however, SMCs were unresponsive to infused bFGF. Infusion of a "mitotoxin" (bFGF conjugated to saporin) caused a greater than 50% decrease in the number of viable SMCs in the arterial wall after balloon injury. Prolonged administration of bFGF (12 micrograms/day for 2 weeks) after balloon injury caused an approximately twofold increase in intimal thickening. These results show that bFGF, which is synthesized by the arterial wall, could be a potent mitogen for SMCs in vivo and suggest that any release of endogenous bFGF may be capable of stimulating SMC proliferation, which may subsequently lead to intimal lesion formation.

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				M. Janiszewski, F. R. M. Laurindo, C. A. Pasqualucci, P. L. da Luz, and F. Pileggi Effects of a Single Heparin Bolus on Neointimal Growth After Arterial Injury in Intact Rabbits Angiology, June 1, 1996; 47(6): 549 - 556. [Abstract] [PDF]

				H. Tanaka, G. Sukhova, D. Schwartz, and P. Libby Proliferating Arterial Smooth Muscle Cells After Balloon Injury Express TNF-{alpha} but Not Interleukin-1 or Basic Fibroblast Growth Factor Arterioscler Thromb Vasc Biol, January 1, 1996; 16(1): 12 - 18. [Abstract] [Full Text]

				T. Meurice, C. Bauters, J.-L. Auffray, B. Vallet, M. Hamon, F. Valero, E. Van Belle, J.-M. Lablanche, and M. E. Bertrand Basic Fibroblast Growth Factor Restores Endothelium-Dependent Responses After Balloon Injury of Rabbit Arteries Circulation, January 1, 1996; 93(1): 18 - 22. [Abstract] [Full Text]

				G. C. Cheng, P. Libby, A. J. Grodzinsky, and R. T. Lee Induction of DNA Synthesis by a Single Transient Mechanical Stimulus of Human Vascular Smooth Muscle Cells : Role of Fibroblast Growth Factor–2 Circulation, January 1, 1996; 93(1): 99 - 105. [Abstract] [Full Text]

				J. Fingerle, R. M.K. Muller, H. Kuhn, M. Pech, and H. R. Baumgartner Mechanism of Inhibition of Neointimal Formation by the Angiotensin-Converting Enzyme Inhibitor Cilazapril : A Study in Balloon Catheter–Injured Rat Carotid Arteries Arterioscler Thromb Vasc Biol, November 1, 1995; 15(11): 1945 - 1950. [Abstract] [Full Text]

				T. Asahara, C. Bauters, L. P. Zheng, S. Takeshita, S. Bunting, N. Ferrara, J. F. Symes, and J. M. Isner Synergistic Effect of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor on Angiogenesis In Vivo Circulation, November 1, 1995; 92(9): 365 - 371. [Abstract] [Full Text]

				K. Futami, J. Yamashita, O. Tachibana, S. Kida, S. Higashi, K. Ikeda, and T. Yamashima Basic Fibroblast Growth Factor May Repair Experimental Cerebral Aneurysms in Rats Stroke, September 1, 1995; 26(9): 1649 - 1654. [Abstract] [Full Text]

				C. Bauters, F. Marotte, M. Hamon, P. Oliviero, F. Farhadian, V. Robert, J. L. Samuel, and L. Rappaport Accumulation of Fetal Fibronectin mRNAs After Balloon Denudation of Rabbit Arteries Circulation, August 15, 1995; 92(4): 904 - 911. [Abstract] [Full Text]

				V. Lindner, C. M. Giachelli, S. M. Schwartz, and M. A. Reidy A Subpopulation of Smooth Muscle Cells in Injured Rat Arteries Expresses Platelet-Derived Growth Factor–B Chain mRNA Circ. Res., June 1, 1995; 76(6): 951 - 957. [Abstract] [Full Text]

				T. Asahara, C. Bauters, C. Pastore, M. Kearney, S. Rossow, S. Bunting, N. Ferrara, J. F. Symes, and J. M. Isner Local Delivery of Vascular Endothelial Growth Factor Accelerates Reendothelialization and Attenuates Intimal Hyperplasia in Balloon-Injured Rat Carotid Artery Circulation, June 1, 1995; 91(11): 2793 - 2801. [Abstract] [Full Text]

				M. A. Parish, E. A. Grossi, F. G. Baumann, T. Asai, D. B. Rifkin, S. B. Colvin, and A. C. Galloway Effects of a Single Administration of Fibroblast Growth Factor on Vascular Wall Reaction to Injury Ann. Thorac. Surg., April 1, 1995; 59(4): 948 - 954. [Abstract] [Full Text]

				M. J.A.P. Daemen and J. G.R. De Mey Regional Heterogeneity of Arterial Structural Changes Hypertension, April 1, 1995; 25(4): 464 - 473. [Abstract] [Full Text]

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				T. Hirozane, A. Matsumori, Y. Furukawa, and S. Sasayama Experimental Graft Coronary Artery Disease in a Murine Heterotopic Cardiac Transplant Model Circulation, January 15, 1995; 91(2): 386 - 392. [Abstract] [Full Text]

				A. A. Soyombo, G. D. Angelini, and A. C. Newby Neointima formation is promoted by surgical preparation and inhibited by cyclic nucleotides in human saphenous vein organ cultures J. Thorac. Cardiovasc. Surg., January 1, 1995; 109(1): 2 - 12. [Abstract] [Full Text]

				A Yanagisawa-Miwa, Y Uchida, F Nakamura, T Tomaru, H Kido, T Kamijo, T Sugimoto, K Kaji, M Utsuyama, C Kurashima, et al. Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor Science, September 4, 1992; 257(5075): 1401 - 1403. [Abstract] [PDF]

				K. Kobuke, Y. Furukawa, M. Sugai, K. Tanigaki, N. Ohashi, A. Matsumori, S. Sasayama, T. Honjo, and K. Tashiro ESDN, a Novel Neuropilin-like Membrane Protein Cloned from Vascular Cells with the Longest Secretory Signal Sequence among Eukaryotes, Is Up-regulated after Vascular Injury J. Biol. Chem., August 31, 2001; 276(36): 34105 - 34114. [Abstract] [Full Text] [PDF]