PMID: 9435591Jan 22, 1998Paper

Heparin/heparan sulfate chelation inhibits control of vascular repair by tissue-engineered endothelial cells

The American Journal of Physiology
R O HanE R Edelman

Abstract

The relative importance of heparin-like compounds in mediating vascular repair is unclear. We investigated how protamine, a chelator of heparin, affected endothelial cell inhibition of vascular smooth muscle cell growth and intimal hyperplasia. The 52% (P < 0.001) reduction in smooth muscle cell proliferation produced by postconfluent endothelial cell-conditioned medium was entirely reversed by pretreatment of medium with heparinase and heparitinase and was inhibited in a dose-dependent fashion by the coadministration of protamine. Pretreatment of conditioned medium with heparinase and heparitinase largely prevented protamine's mitogenic activity, suggesting that protamine affects growth by interacting with heparin-like compounds. Perivascular implantation of polymerengrafted endothelial cells reduced neointima formation in denuded rat carotid arteries by 92% (P < 0.001) and cell proliferation by 81% (P < 0.001). Coadministration of protamine abolished the inhibitory potential of the cell implants, resulting in a nearly twofold exacerbation of intimal hyperplasia compared with controls (P < 0.001). Thus heparin-like molecules are essential to the biochemical regulation of vascular repair provided by endothelial cells, and the c...Continue Reading

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Citations

Jun 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·D BerryR Sasisekharan
Aug 29, 2006·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Anastasia Z KaleaDorothy J Klimis-Zacas

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