This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Medalion, B. Articles by Vlodavsky, I. Search for Related Content PubMed PubMed Citation Articles by Medalion, B. Articles by Vlodavsky, I. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Thinners Hazardous Substances DB HEPARIN

(Circulation. 1997;95:1853-1862.)
© 1997 American Heart Association, Inc.

Articles

Endogenous Basic Fibroblast Growth Factor Displaced by Heparin From the Lumenal Surface of Human Blood Vessels Is Preferentially Sequestered by Injured Regions of the Vessel Wall

Benjamin Medalion, MD; Gideon Merin, MD; Helena Aingorn, PhD; Hua-Quan Miao, MD; Arnon Nagler, MD; Amir Elami, MD; Rivka Ishai-Michaeli, MSc; Israel Vlodavsky, PhD

From the Departments of Thoracic and Cardiovascular Surgery (B.M., G.M., A.E.), Oncology (H.A., H.-Q.M., R.I.-M., I.V.), and Bone Marrow Transplantation (A.N.), Hadassah-Hebrew University Hospital, Jerusalem, Israel.

Correspondence to Dr Israel Vlodavsky, Department of Oncology, Hadassah Hospital, POB 12000, Jerusalem, 91120, Israel.

Background Proliferation of smooth muscle cells (SMCs) of the arterial wall in response to local injury is an important factor in vascular proliferative disorders. Among the growth factors that promote SMC proliferation is basic fibroblast growth factor (bFGF), which is characterized by a high affinity for heparin and is associated with heparan sulfate on cell surfaces and extracellular matrices. We investigated whether heparin can displace endogenous active bFGF from the lumenal surface of blood vessels, whether bFGF is preferentially bound to injured blood vessels, and whether a synthetic, polyanionic, heparin-mimicking compound (RG-13577) can prevent sequestration of bFGF by the vessel wall.

Methods and Results Injured and noninjured saphenous vein segments were perfused with or without heparin, in the absence or presence of ¹²⁵I-bFGF and/or RG-13577 (a polymer of 4-hydroxyphenoxy acetic acid). Heparin displaced bFGF from the lumenal surface of the vein, and the released bFGF stimulated proliferation of SMCs. Likewise, systemic administration of heparin during open heart surgery resulted in a marked increase in plasma bFGF levels. Injured veins sequestered ¹²⁵I-bFGF to a much higher extent than noninjured vein segments, both in the absence and presence of heparin. This sequestration was inhibited by compound RG-13577.

Conclusions Despite its beneficial effects, heparin may displace active bFGF, which subsequently may be preferentially deposited on injured vessel walls, thus contributing to the pathogenesis of restenosis. This effect may be prevented by a synthetic heparin-mimicking compound.

Key Words: heparin • growth inhibitory substances • veins • cells, smooth muscle

This article has been cited by other articles:

				A. Sahni, A. A. Khorana, R. B. Baggs, H. Peng, and C. W. Francis FGF-2 binding to fibrin(ogen) is required for augmented angiogenesis Blood, January 1, 2006; 107(1): 126 - 131. [Abstract] [Full Text] [PDF]

				G. S. Werner, E. Jandt, A. Krack, G. Schwarz, O. Mutschke, F. Kuethe, M. Ferrari, and H. R. Figulla Growth Factors in the Collateral Circulation of Chronic Total Coronary Occlusions: Relation to Duration of Occlusion and Collateral Function Circulation, October 5, 2004; 110(14): 1940 - 1945. [Abstract] [Full Text] [PDF]

				N. Auge, O. Rebai, J. Lepetit-Thevenin, N. Bruneau, J.-C. Thiers, E. Mas, D. Lombardo, A. Negre-Salvayre, and A. Verine Pancreatic Bile Salt-Dependent Lipase Induces Smooth Muscle Cells Proliferation Circulation, July 8, 2003; 108(1): 86 - 91. [Abstract] [Full Text] [PDF]

				Q. ESCARTIN, C. LALLAM-LAROYE, B. BAROUKH, F. O. MORVAN, J. P. CARUELLE, G. GODEAU, D. BARRITAULT, and J. L. SAFFAR A new approach to treat tissue destruction in periodontitis with chemically modified dextran polymers FASEB J, April 1, 2003; 17(6): 644 - 651. [Abstract] [Full Text] [PDF]

				P. Lambiase, R. Edwards, C. A. Bucknall, M. S. Marber, C. Seiler, M. Fleisch, M. Billinger, F. R. Eberli, A. R. Garachemani, and B. Meier Physiologically Assessed Collateral Flow and Intracoronary Growth Factor Concentrations in Patients With 1- to 3-Vessel Coronary Artery Disease Response Circulation, January 30, 2001; 103 (4): e22 - e22. [Full Text] [PDF]

				D. J. Phillips, K. L. Jones, D. J. McGaw, N. P. Groome, J. J. Smolich, H. Pärsson, and D. M. de Kretser Release of Activin and Follistatin during Cardiovascular Procedures Is Largely due to Heparin Administration J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2411 - 2415. [Abstract] [Full Text]

				D. N. Rhoads, S. G. Eskin, and L. V. McIntire Fluid Flow Releases Fibroblast Growth Factor-2 From Human Aortic Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2000; 20(2): 416 - 421. [Abstract] [Full Text] [PDF]

				M. Fleisch, M. Billinger, F. R. Eberli, A. R. Garachemani, B. Meier, and C. Seiler Physiologically Assessed Coronary Collateral Flow and Intracoronary Growth Factor Concentrations in Patients With 1- to 3-Vessel Coronary Artery Disease Circulation, November 9, 1999; 100(19): 1945 - 1950. [Abstract] [Full Text] [PDF]

				J. R. Sindermann and K. L. March Heparin Responsiveness In Vitro as a Prognostic Tool for Vascular Graft Stenosis : A Tale of Two Cell Types? Circulation, June 30, 1998; 97(25): 2486 - 2490. [Full Text] [PDF]

				A. Sahni, T. Odrljin, and C. W. Francis Binding of Basic Fibroblast Growth Factor to Fibrinogen and Fibrin J. Biol. Chem., March 27, 1998; 273(13): 7554 - 7559. [Abstract] [Full Text] [PDF]