Increase in the growth inhibition of bovine pulmonary artery smooth muscle cells by an O-hexanoyl low-molecular-weight heparin derivative

Hari G. Garg, Charles A. Hales, Lunyin Yu, Melissa Butler, Tasneem Islam, Jin Xie, Robert J. Linhardt

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Proliferation of pulmonary artery smooth muscle cells (PASMCs) appears to play a significant role in chronic pulmonary hypertension. The proliferation of PASMCs is strongly inhibited by some commercial heparin preparations. Heparin fragments were prepared by periodate treatment, followed by sodium borohydride reduction, to enhance potency. The tributylammonium salt of this fragmented heparin was O-acylated with hexanoic anhydride. Gradient polyacrylamide gel electrophoresis showed that the major heparin fragment contained eight disaccharide units. NMR analysis showed that approximately one hexanoyl group per disaccharide residue was present. The O-hexanoyl heparin fragments were assayed for growth inhibitory effect on bovine PASMCs in culture. This derivative was found to be more effective in growth inhibition of bovine PASMCs in culture than the heparin from which it was derived. In the future, it is envisioned that this or similar derivatives may be an effective treatment for pulmonary hypertension.

Original languageEnglish
Pages (from-to)2607-2612
Number of pages6
JournalCarbohydrate Research
Volume341
Issue number15
DOIs
StatePublished - 6 Nov 2006
Externally publishedYes

Keywords

  • O-Hexanoyl heparin
  • Pulmonary artery smooth muscle cell proliferation

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