Gene interactions and pathways from curated databases and text-mining
Vascul Pharmacol 2006, PMID: 16600694

Aspirin and PPAR-alpha activators inhibit monocyte chemoattractant protein-1 expression induced by high glucose concentration in human endothelial cells.

Dragomir, Elena; Tircol, Magdalena; Manduteanu, Ileana; Voinea, Manuela; Simionescu, Maya

Activated endothelial cells express monocyte chemoattractant protein-1 (MCP-1), a chemokine which is reportedly involved in the recruitment of plasma monocytes in the early stages of atherosclerosis. Since accelerated atherosclerosis is the main complication of diabetes and both diseases encompass an inflammatory reaction, we hypothesized that the anti-inflammatory drugs, aspirin and peroxisome proliferator-activated receptor (PPAR-alpha) activators (fenofibrate and clofibrate), could have an effect on the high glucose-induced MCP-1 expression in endothelial cells. To test this assumption, as well as the possible mechanisms involved, the MCP-1 expression and secretion, the reactive oxygen species levels, nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) expression were determined in human endothelial cells exposed to high glucose concentrations in the presence of aspirin, fenofibrate and clofibrate. Human endothelial cells kept in normal glucose concentration in the absence of drugs were used as control. The results showed that (i) aspirin, fenofibrate and clofibrate decrease significantly the MCP-1 expression and secretion in human endothelial cells; (ii) the high glucose up-regulated expression of MCP-1 in endothelial cells was significantly reduced by inhibitors of NF-kB and reactive oxygen species; (iii) all drugs notably decrease the level of the reactive oxygen species and activation of NF-kB and AP-1. Together, the findings indicate that in endothelial cells aspirin and PPAR-alpha activators reduce the high glucose-increased expression of MCP-1 by a mechanism that includes the inhibition of reactive oxygen species, and decrease of AP-1 and NF-kB activation.

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Text Mining Data

monocyte chemoattractant protein-1 ⊣ PPAR-alpha: " Aspirin and PPAR-alpha activators inhibit monocyte chemoattractant protein-1 expression induced by high glucose concentration in human endothelial cells "

MCP-1 ⊣ PPAR-alpha: " Together, the findings indicate that in endothelial cells aspirin and PPAR-alpha activators reduce the high glucose increased expression of MCP-1 by a mechanism that includes the inhibition of reactive oxygen species, and decrease of AP-1 and NF-kB activation "

NF-kB → AP-1: " Together, the findings indicate that in endothelial cells aspirin and PPAR-alpha activators reduce the high glucose increased expression of MCP-1 by a mechanism that includes the inhibition of reactive oxygen species, and decrease of AP-1 and NF-kB activation "

Manually curated Databases

No curated data.