Von Willebrand factor deficiency and atherosclerosis.

Von Willebrand factor (VWF) is a large multimeric glycoprotein that plays a major role in haemostasis, illustrated by the bleeding tendency in von Willebrand disease (VWD), the most common hereditary bleeding disorder caused by VWF deficiency or dysfunction. Elevated VWF levels are strongly associated with an increased risk of ischemic cardiovascular events. Whether this relation is causal, or whether increased VWF levels reflect disturbances of endothelial function remains to be elucidated. One possibility is that VWF participates in the process of atherogenesis. The aim of the current review is to determine whether VWF deficiency provides protection against the development of atherosclerosis in humans and animals. Results from animal studies suggest that, at arterial branch point predilection sites, VWF deficiency or blockage has a protective effect against atherosclerosis. Based on the available evidence, this potential protective effect of VWF deficiency can most likely be tracked to the VWF-platelet interaction. Sites involved in this interaction could prove attractive targets in future treatment and prevention of cardiovascular disease, an option that is already being explored in humans. An unequivocal protective effect of VWD on atherosclerosis has not been demonstrated in humans. However the interpretation of these results is hampered by several methodological weaknesses. In conclusion, VWF is probably a significant player in the multifaceted interaction between the haemostatic system and the atherosclerotic process which deserves further study.

Effects of suramin on cell-cycle kinetics of MCF-7 human breast cancer cells in vitro.

The polyanionic compound suramin can inhibit the proliferation of cells of various origin, including from breast cancer. We have studied the effects of suramin on cell cycle kinetics and distribution of MCF-7 human breast cancer cells in vitro. It was found that both under serum-containing and serum-free culture conditions, and in the absence or presence of oestradiol or insulin-like growth factor-1, prolonged exposure (> or = 48 h) to suramin caused an accumulation of surviving cells in the G2/M-phase of the cell cycle. At a concentration of more than 100 micrograms ml-1 suramin significantly inhibited cell proliferation. The observed effects of suramin on breast cancer cells in vitro, i.e. antiproliferative effects and accumulation of cells in the G2/M-phase of the cell cycle, may have beneficial consequences in the application of treatment strategies based on a combination of suramin with cell cycle specific drugs or radiation therapy.

Pleiotropic actions of suramin on the proliferation of human breast-cancer cells in vitro.

Suramin, a non-specific growth factor antagonist, is currently under investigation for treatment of cancer patients. We studied its action on 6 different human breast-cancer cell lines in vitro. In complete growth medium, pleiotropic effects were observed with respect to cell proliferation, i.e. suramin is stimulatory at low concentrations and inhibitory at higher concentrations, for 4 of the 6 cell lines studied. The various cell lines showed marked differences with respect to the antiproliferative action of suramin, the Evsa-T cells being by far the most sensitive ones. A suramin concentration of 100 micrograms/ml brought about a 100% stimulation of the proliferation of ZR/HERc cells, ZR 75.1 cells ectopically expressing a human epidermal growth factor receptor (EGF-R) cDNA. Although less pronounced (10 to 60% stimulation), a similar response was observed for the parent ZR 75.1 cells, as well as for T-47D and MDA-MB-231 cells. The non-specificity of the action of suramin was established by the observation that suramin-induced inhibition of cell proliferation could be abolished by insulin-like growth factor-I (IGF-I) or basic fibroblast growth factor (bFGF), and even by estradiol, both in complete growth medium and under defined serum-free conditions. Our data indicate that suramin exerts pleiotropic effects on the proliferation of human breast cancer cells in vitro, and confirm the non-specific nature of its action. The stimulatory effect of low concentrations of suramin on the proliferation of breast cancer cells may have important consequences for breast cancer patients treated with suramin.