Inhibitory effect of functional dextrans on rat arterial smooth muscle cell growth in vitro

Abstract

Derivatized dextrans substituted with carboxylic, benzylamide and sulfonate groups were tested in vitro for their antiproliferative activity on arterial rat smooth muscle cells (SMCs). Some of these sulfated polysaccharides, without potent anticoagulant activity, exhibit an inhibitory effect on cell growth as effective as heparin. A study of different molecular weight fractions, from 4000 to 180000g mol −1 obtained by gel filtration chromatography, shows that this inhibitory effect disappears below about 65 osidic units. The action of these sulfated polysaccharides is a time-dependent event which blocks the cell cycle at the G 0 G 1 phase with the largest effect exhibited during the first 4 h. From the kinetics of DNA synthesis experiments, it appears that the antiproliferative effect is caused by a delay in cells entering the S phase from the G 0 G 1 phase. Because these compounds have low anticoagulant activity and are non-cytotoxic, they may represent an inexpensive source of new types of agent to suppress intimai SMC hyperplasia.