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Structural determinants of the capacity of heparin to inhibit the proliferation of vascular smooth muscle cells
Author(s) -
Castellot John J.,
Karnovsky Morris J.,
Beeler David L.,
Rosenberg Robert D.
Publication year - 1984
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041200309
Subject(s) - heparin , vascular smooth muscle , cell growth , in vitro , anticoagulant , in vivo , glycosaminoglycan , chemistry , microbiology and biotechnology , smooth muscle , sulfation , function (biology) , biochemistry , pharmacology , biology , endocrinology , medicine
Previous work from our laboratory has demonstrated that both anticoagulant and nonanticoagulant heparin species can inhibit the proliferation of vascular smooth muscle cells in vivo and in vitro. In this communication, we report studies on the structure‐function relationships of heparin to its antiproliferative effect on vascular smooth muscle cells. These structure‐function studies were carried out by preparing discrete sizes of heparin fragments and by chemically modifying heparin. The compounds were tested for their ability to inhibit rat and calf aortic smooth muscle cell growth. The minimum fragment size which retains some growth inhibitory activity is a hexasaccharide; maximal antiproliferative activity was obtained with dodecasaccharide and larger fragments. Both O‐sulfation and N‐substitution were found to be important for the growth inhibitory effect. Comparison of the antiproliferative and anticoagulant activities of the different heparin species has allowed us to identify several heparin molecules which have lost their anticoagulant properties, but retain antiproliferative activity.