title: Inhibition of smooth muscle cell proliferation and neointimal growth by low-anticoagulant heparin.
abstract: Low-anticoagulant heparin (LA-heparin) obtained by affinity chromatography on antithrombin III Sepharose inhibits the proliferation of cultured arterial smooth muscle cells in an in vitro bioassay system as effectively as standard heparin. A growth inhibition of smooth muscle cells of about 60% is achieved when LA-heparin or heparin is added to the culture medium to a concentration of 50 micrograms/ml. In normolipemic rats LA-heparin suppresses the formation of neointimal thickenings and stenosis after balloon catheter-induced deendothelialization of the carotid artery. In terms of mass a dose of 5 mg/kg body weight/d given subcutaneously twice daily one week before and 2 weeks after balloon injury the cross sectional area of the neointima is reduced to 36% as compared with the nontreated control group (100%). This 64% reduction is statistically highly significant (p < 0.001). After treatment with 0.5 mg LA-heparin/kg/d the reduction of the neointima was 11% (p < 0.05). At a dose of 5 mg/kg body weight single or repeated administrations of LA-heparin caused only a small and transient increase in activated partial thromboplastin time values. The results show that subcutaneous administration of LA-heparin very effectively prevents smooth muscle cell proliferation and balloon catheter-induced neointimal growth. The well tolerated systemic application of this chemically non-modified LA-heparin might justify clinical trials for prevention of restenosis after percutaneous transluminal coronary angioplasty or other invasive cardiovascular interventions without complications of bleeding.
authors.affiliation: Institute for Arteriosclerosis Research, University of Münster, Münster/Westf, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Völker
authors.forename: A
authors.initials: A
authors.lastname: Böhm
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: C M
authors.initials: CM
authors.lastname: Svahn
authors.forename: A K
authors.initials: AK
authors.lastname: Gellerbring
authors.forename: C
authors.initials: C
authors.lastname: Mattsson
authors.forename: S
authors.initials: S
authors.lastname: Ekvärn
authors.forename: H
authors.initials: H
authors.lastname: Robenek
authors.forename: E
authors.initials: E
authors.lastname: Buddecke
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002339:Carotid Arteries / Q000166:cytology / Q000187:drug effects; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000925:Anticoagulants; D006493:Heparin