Rat Arterial Smooth Muscle Cell Research Articles

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

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.

Prevention of stenosis after vascular reconstruction: Pharmacologic control of intimal hyperplasia — A review

Prevention of stenosis after vascular reconstruction: Pharmacologic control of intimal hyperplasia — A review

In vitro inhibition of rat arterial smooth muscle cell growth by extractive sulfated mucopolysaccharides

The effect of a sulfared mucopolysaccharide mixture of known composition, extracted from pig duodenum, was studied on the proliferation of rat arterial smooth muscle cells cultured from rat aorta. Cell growth, stimulated by fetal calf serum, was monitored by direct cell count and by determination with commercial heparin, with heparin with different electrophoretic mobilities in barium acetate and with dermatan and heparan sulfates. Heparins and the extractive mucopolysaccharide mixture inhibited cell growth measured at various time intervals, and in their presence the proliferation of smooth muscle cells plateaued at lower cell densities. Dermatan and heparan sulfates were either inactive or significantly less effective than the other mucopolysaccharides. A short preincubation (3 h) of smooth muscle cells with the extractive mixture, followed by incubation with the growing medium with no mucopolysaccharides added, slowed the cell growing rate, suggesting an interaction of the mixture components with the cell surface.

Inhibition of rat arterial smooth muscle cell proliferation by heparin. II. In vitro studies.

We studied in vitro the effects heparin on the growth of rat aortic smooth muscle cells. Measurements of growth were monitored by [3H]thymidine uptake and changes in cell number over a period of 3 days. Our results show that heparin-highly anticoagulant or nonanticoagulant-significantly inhibits growth of smooth muscle cells. We also show that this is a highly specfic interaction with regard to molecule and cell type: i.e., other polyanions, except for a low molecular weight dextran sulfate, do not have the same effect on growth, and not all cells are inhibited by heparin; e.g., endothelial cell growth actually is enhanced. After removing antithrombin from our media, we carried out experiments which show that heparin is effective even though thrombin, a potent mitogenic agent, is still present and active. We also found that passing the platelet extract over a heparin column did not remove all of the motogenic activity of the platelet preparation. Both experiments indicate an inhibitory role for the heparin molecule, per se. Our results support the findings of a recent paper (Guyton et al., 1980) showing that heparin can limit the size of myointimal plaques in rats after carotid injuries by inhibiting smooth muscle cell proliferation.

Inhibition of rat arterial smooth muscle cell proliferation by heparin. In vivo studies with anticoagulant and nonanticoagulant heparin.

Inhibition of rat arterial smooth muscle cell proliferation by heparin. In vivo studies with anticoagulant and nonanticoagulant heparin.

The effect of insulin and glucose on sterol synthesis in cultured rat arterial smooth muscle cells

The smooth muscle cell plays an important role in the process of atherogenesis, proliferating in the arterial intima and becoming filled with lipid during the course of the disease. In these experiments the effect of insulin and glucose on sterol synthesis in cultured rat arterial smooth muscle cell was studied. Arterial smooth muscle cells were cultured from pieces of intima and inner media of young rat aortas. The cells were grown in Petri dishes in culture medium with foetal calf serum and when confluent were exposed to insulin or glucose for 24 hours. Insulin in concentrations of 10 μU-100 mU per ml stimulated the incorporation of sodium [2- 14C]acetate into non-saponifiable lipids and digitonin precipitable sterols. However, insulin had no effect on the incorporation of labelled mevalonate into cell sterols. Increasing concentrations of glucose in the medium up to 140 mM had had no effect on the incorporation of isotope into sterols, but higher concentrations of glucose caused cell damage and sterol synthesis was markedly depressed. These results may have relevance to the development of atherosclerosis in diabetes and obesity.