Gene expression and intracellular pathways involved in XXXX induced by VLDL and oxidised VLDL.

@entity1 @entity2451 @entity1476 @entity310 @entity26 @entity409 @entity6785 @entity10366 @entity412 @entity3053 @entity8252 @entity453 @entity1366
OBJECTIVES: The molecular mechanisms underlying the relationship between elevated plasma concentrations of @entity412 -rich lipoproteins and @entity453 remain uncertain. In the present work, we investigated the gene expression pattern and intracellular pathways in @entity1 endothelial cells incubated with very low density lipoproteins (VLDL). Moreover, as VLDL can enter the arterial wall and undergo oxidative modification, we compared the VLDL-induced expression pattern with the one of oxidised VLDL (Ox-VLDL). METHODS: Total RNA from endothelial cells incubated with 75 microg/ml VLDL or Ox-VLDL and total RNA from endothelial cells under basal conditions were hybridised to identical microarrays containing 8411 genes. Seven clusters of expression profiles were identified. This pattern was validated by quantitative real-time PCR of selected genes. The intracellular pathway involved in VLDL or Ox-VLDL mediated endothelial responses were also investigated. RESULTS AND CONCLUSION: VLDL predominantly activated the @entity1366 pathway while P38 MAPK was the main target of Ox-VLDL. @entity10366 and @entity2451 were activated by both VLDL and Ox-VLDL. Real-time PCR demonstrated that VLDL induced @entity1476 (5.47+/-1.74 fold), @entity3053 (2.38+/-0.23) and @entity310 (2.51+/-0.30) expression. Ox-VLDL was found to induce @entity8252 (2.10+/-0.48) and @entity6785 (3.19+/-0.07) expression. In addition, several genes implicated in endothelial cell activation and damage/proliferation were identified by the array analysis. Ox-VLDL was found to promote the generation of reactive @entity26 species and exert a cytotoxic effect, while VLDL lacks these effects. These findings confirm the involvement of VLDL and Ox-VLDL in @entity409 and suggest new genes and molecular mechanisms involved in these actions.
