Antiproliferative effect endothelial cells

The physiological function of heparin is not completely understood. It is found only in trace amounts in normal circulating blood. It exerts an antihpemic effect by releasing lipoprotein lipase from endothehal cells heparinlike proteoglycans produced by endothelial cells have anticoagulant activity. Heparin decreases platelet and inflammatory cell adhesiveness to endothelial cells, reduces the release of platelet-derived growth factor, inhibits tumor cell metastasis, and exerts an antiproliferative effect on several types of smooth muscle. 

Apart from its potent antiproliferative activity, tetrasaccharide 15 was effective in blocking human complement in vitro and inhibited the release of heparan sulfate from cardiac microvascular endothelial cells. To overcome hyperacute rejection, the tetrasaccharide has been investigated in a guinea pig to rat cardiac xenotransplantation model and significantly prolonged the survival of heart recipients when compared to control and heparin treated groups [46]. 

S-allylmercaptocysteine (SAMC), was susceptible to the growth-inhibitory influence of the two hormone-responsive cancer cell lines of breast and prostate MCF-7 and CRL-1740, respectively. The antiproliferative effect of SAMC was limited to actively growing cells. Human umbilical vein endothelial cells diat had reached confluence escaped the reduction in viability so noticeable in the cancer cell lines tested [80]. 

The effect of fucoidan from A. nodosum on fibroblast growth factor (FGF)-2-induced proliferation and differentiation of human umbilical vein endothelial cells (Matou et al., 2002) was reported. Their results showed that fucoidan can enhance vascular tube formation induced by FGF-2 with a modulation of the expression of surface proteins involved in angiogenesis. In another study, however, smooth muscle cell proliferation was inhibited by fucans, suggesting an antiproliferative effect (Logeart et al., 1997). Together with these results, Matou et al. (2002) suggested a potential preventive effect of fucoidan on restenosis. 

In human arterial endothelial cells, L-ascorbic acid, alone or in combination with a-tocopherol-induced proliferation and DNA synthesis and antagonized the antiproliferative effects of oxLDL, bnt in VSMC the proliferation is inhibited (Ulrich-Merzenich et al. 2002). The ECM may contribute to the inhibition of DNA synthesis and proliferation, since VSMC plated on extracellular matrices deposited by VSMC in the presence of 0.1-1 mM L-ascorbic acid had an up to 50% lower proliferation rate than on matrices from L-ascorbic acid-deficient cells (Ivanov et al. 1997). The inhibitory effect is not specific for the biological active isomer of L-ascorbic acid, and isoascorbate and D-ascorbic acid are even more effective in reducing cell growth than L-ascorbic acid (Alcain and Buron 1994). 

Caffeic Acid Phenethyl Ester (CAPE). CAPE, a phenolic compound with antioxidant properties, is an active ingredient derived from honeybee propolis (52). CAPE has antiviral, anti-inflammatory and antiproliferative properties. The compound differentially suppresses the growth of numerous human cancer cells and also inhibits tumor promoter-mediated processes in transformed cells (53,54). In transformed cells, CAPE induces apoptosis and inhibits the expression of the malignant phenotype (55,56). In addition, CAPE treatment attenuates the formation of azoxymethane-induced aberrant crypts and the activities of ornithine decarboxylase (ODC), tyrosin protein kinase, and lipoxygenase activity (57). Although the molecular basis for these multiple chemopreventive effects of CAPE is not clear, recent studies have demonstrated that CAPE is a potent and specific inhibitor of the transcription factor NF-kB (58). CAPE inhibited the activity and expression of COX-2 in the carrageenan air pouch model of inflammation as well as in TPA-treated human oral epithelial cells (59). CAPE was able to reduce neointimal formation by inhibiting NF-kB activation in a model of endothelial injury of rat carotid artery (60). 

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