Endothelial activation inhibition

Carluccio, M.A., Siculella, L., Ancora, M.A., Massaro, M., Scoditti, E., Storelli, C., Visioli, F., Distante, A., and De Caterina, R., Olive oil and red wine antioxidant polyphenols inhibit endothelial activation antiatherogenic properties of mediterranean diet phytochemicals, Arterioscler. Thromb. Vase. Biol, 23, 622, 2003. 

Cheng, N., Brantley, D. M., Liu, H., Lin, Q., Enriquez, M., et al. 2002. Blockade of EphA receptor tyrosine kinase activation inhibits vascular endothelial cell growth factor-induced angiogenesis. Mol. Cancer Res. 1 2-11. 

Stehlik C, de Martin R, Kumabashiri I, Schmid JA, Binder BR, Lipp J (1998) Nuclear factor (NF)-kappaB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis. J Exp Med 188 211-216 Stennicke HR, Deveraux QL, Humke EW, Reed JC, Dixit VM, Salvesen GS (1999) Caspase-9 ctin be activated without proteolytic processing. J Biol Chem 274 8359-8362 Sun XM, Butterworth M, MacFarlane M, Dubiel W, Ciechanover A, Cohen GM (2004) Caspase activation inhibits proteasome function during apoptosis. Mol Cell 14 81-93 Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R (2001) A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell 8 613-621... 

Protein kinase C (PKC) has been implicated in the regulation of NO production in endothelial cells. Castro et al. (1998) reported that in porcine aortic endothelial cells ATP induced increase in NO production was mediated via activation of PKC [32]. There are, however, reports of PKC mediated inhibition of eNOS via phosphorylation in BAEC treated with a phorbol ester [33] as it has been demonstrated that PKC activation inhibits eNOS activity by phosphorylating at threonine 495 and dephosphorylating at serine 1177 [34]. Unlike PKC, activation of eNOS by PKA occurs via phosphorylation of the enzyme at serine 1177 and de-phosphorylation at threonine 495 [34] (see Figure 2). 

There are most likely a number of diverse molecular pathways by which NO can alter gene expression, but in the case of MCP-1 this pathway has been partially elucidated. In human endothelial cells inhibition of NO synthesis has been shown to activate proteins capable of binding to oligonucleotides containing the NF-kB binding site (Zeiher etal., 1995), suggesting a molecular link between an oxidant-sensitive transcriptional regulatory mechanism and NO synthesis. However, it cannot be excluded that NO also influences the activation of other transcription factors, such as AP-1, which has recently been characterized as an antioxidant-responsive factor (Meyer et al., 1993). Indeed, in in vitro gel-mobility assays the NO donor sodium nitroprusside, but no free NO, has been reported to S-nitrosylate the AP-1 moiety and inhibit its activity (Tabuchi et al., 1994). 

Attracts CLA+ T cells and directs them into the skin Attracts lymphocyte subsets during inflammation facilitates certain immune response Stimulates proliferation of epidermal and epithelial cells inhibits gastric secretion involves in wound healing Induces proliferation and migration fenestration in capillary endothelial cells Inhibits endothelial cell proliferation, vasculogenesis, neovessel formation inhibits angiogenesis of vascular beds suppresses tumor growth induces apoptosis and myeloperoxidase activity from neutrophils... 

Redmond, E. M., Cullen, J. P., Cahill, P. A., etal, Endothelial cells inhibit flow-induced smooth muscle cell migration Role of plasminogen activator inhibitor-1. Circulation 103, 597-603 (2001). 

Marx N, Sukhova GK, Collins T, Libby P, Plutzky J (1999) PPARalpha activators inhibit cytokine-induced vascular ceU adhesion molecule-1 expression in human endothelial cells. Circulation 99 3125-3131... 

EGCG and quercetin Human umbilical vein endothelial cells Inhibited endothelial apoptosis enhanced the expression of Bcl-2 protein and inhibited the expression of Bax protein and the cleavage and activation of caspase-3. [76] ... 

Marx, N., Mach, F., Sauty, A., Leung, J. H., Sarafi, M. N., Ransohoff, R. M., Libby, P., Plutzky, J., and Luster, A. D. (2000). Peroxisome proliferator-activated receptor-y activators inhibit IFN-y-induced expression of the T-cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells. J. Immunol. 164, 6503-6508. 

Carluccio MA et al (2003) Olive oil and red wine antioxidant polyphenols inhibit endothelial activation antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscler Thromb Vase Biol 23 622-629... 

Delerive P, Martin-Nizard F, Chinetti G, et al. PRAR activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the AP-1 signaling pathway. Circ Res 1999 85 394-402. 

Stimulate neutrophil O2 free radical formation stimulate lymphocyte proliferation stimulate PAF express intercellular adhesion molecule-1 on endothelial cells inhibit plasminogen activator, thus, procoagulants Stimulates the synthesis of all phase proteins involved in the inflammatory response C-reative protein serum amyloid A fibrinogen oi-chymotrypsin and haptoglobin... 

Carretero, J., Obrador, E., Esteve, J.M., Ortega, A., Pellicer, J.A., Sempere, F.V., and Estrela, J.M. (2001). Tumoricidal activity of endothelial cells. Inhibition of endothelial nitric oxide production abrogates tumor cytotoxicity induced by hepatic sinusoidal endothelium in response to B16 melanoma adhesion in vitro. J. Biol. Chem. 276(28), 25775-25782. 

Systematic screening experiments have identified more than 100 synthetic compounds with potent antiangiogenic activity. The mode of action for most of these molecules is not well understood, but some of the 40 compounds are well advanced in clinical trials (Table 3). The first substance to have entered clinical trials was the Fumagillin-derivative AGM 1470. Fumagillin is an antibiotic which inhibits bFGF- and PDGF-induced endothelial cell proliferation. The mechanism of action of AGM 1470 is poorly understood, but it was shown that it binds and inhibits the metalloprotease methionine aminopeptidase (MetAp-2). 

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