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, Gideon Merin, Helena Aingorn, Hua Quan Miao, Arnon Nagler, Amir Elami, Rivka Ishai-Michaeli, Israel Vlodavsky

Research output: Contribution to journalArticlepeer-review

Abstract

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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1853-1862
Number of pages10
JournalCirculation
Volume95
Issue number7
DOIs
StatePublished - 1 Apr 1997
Externally publishedYes

Keywords

  • cells, smooth muscle
  • growth inhibitory substances
  • heparin
  • veins

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