Ype counterparts (Heymans et al. 1999). IL-8 can be a CXC chemokine generated within a considerable amounts by endothelial cells (Jozkowicz et al. 2001). It really is a proinflammatory and proangiogenic factor, whose effects are mostly exerted by the chemotactic activity toward polymorphonuclear cells. IL-8 production is elevated in atherosclerosis and statins have already been reported to decrease IL-8 synthesis both in vitro (Rezaie-Majd et al. 2003) and in vivo (Waehre et al. 2003). Recent information indicate also that IL-8 exerts direct proangiogenic activity on endothelial cells, by stimulation of their proliferation and inhibition from the starvation-induced apoptosis (Li et al. 2003). Thus, inhibitory impact of atorvastatin on IL-8 production might contribute towards the antiangiogenic activities of statins at micromolar concentrations. In addition to influencing angiogenesis, the decrease within the production of IL-8 can exert antiinflammatory activity. This effect may possibly add for the attenuation of inflammation brought on by lower in PAI-1 synthesis (Wiesbauer et al. 2002). Similar effect on PAI-1 has been observed in our study. Interestingly, we’ve observed for the first time that TSP-1 expression in endothelial cells is decreased in cells treated with atorvastatin, and this impact has been already observed at 100 nM concentration. TSP-1 is called inhibitor of angiogenesis as well as the progression ofEndothelium. Author manuscript; readily available in PMC 2006 March 13.Dulak et al.Pagetumors is dependent on down-regulation of TSP-1 and TSP-2 (AChE Antagonist drug Lawler and Detmar 2004; de Fraipont et al. 2001). Therefore, inhibition of TSP-1 expression could result in enhancement of angiogenesis. Hypoxia was also shown to inhibit TSP-1 generation (PKCθ Purity & Documentation Laderoute et al. 2000). Inhibition of TSP-1 expression is therefore regarded as proangiogenic whereas TSP-1 overexpression as antiangiogenic (Weinstat-Saslow et al. 1994). As a result, it might be surprising that down-regulation of TSP-1 expression by atorvastatin is paralleled by the inhibition of angiogenic activity of endothelial cells. However, this again points towards the complexity of statin-dependent regulation of angiogenic gene expression and angiogenic activity of endothelial cells. It must be noticed, nevertheless, that a stimulatory effect of hypoxia on TSP-1 expression in cultured endothelial cells has been also reported (Phelan et al. 1998). Similarly, the part of TSP-1 in tumor development continues to be enigmatic. It has been for instance shown that the expression of TSP-1 and TSP-2 was significantly increased in invasive breast carcinoma as compared to benign or regular tissue (Bertin et al. 1997; Wang-Rodriguez et al. 2003). Hence, inhibition of TSP-1 synthesis may be also regarded as as useful, at least in certain kinds of tumors. This has been demonstrated in advanced epithelial ovarian carcinoma or breast cancer, even though that effect of TSP-1 down-regulation might not be necessarily related for the angiogenesis (Clezardin et al. 1993). Also, low-microgram concentration of TSP-1 have been reported to be proangiogenic, whereas greater, i.e., more than 25 g/mL per ml are claimed to be antiangiogenic (Motegi et al. 2002). TSP-1 has been also shown to boost uPA and PAI-1 and market metastasis of breast cancer cells (Arnoletti et al. 1995). Therefore, further studies should elucidate what’s the part of TSP-1 inside the growth and angiogenesis of precise varieties of tumors. Ultimately, macroarray analysis, which demonstrated the adjustments in PAI-1 and TSP-1 expression, revea.