Increase in the growth inhibition of bovine pulmonary artery smooth muscle cells by an O-hexanoyl low-molecular-weight heparin derivative.
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.
Garg
Hari G
HG
Department of Medicine, Pulmonary/Critical Care unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. hgarg@partners.org
Hales
Charles A
CA
Yu
Lunyin
L
Butler
Melissa
M
Islam
Tasneem
T
Xie
Jin
J
Linhardt
Robert J
RJ
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry* / Q000494:pharmacology*; D006976:Hypertension, Pulmonary; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology* / Q000187:drug effects
D006495:Heparin, Low-Molecular-Weight