Biochemical and Biophysical Research Communications
PPAR activators inhibit endothelial cell migration by targeting Akt
Section snippets
Methods
Materials. Medium 199 Earle and fetal calf serum (FCS) were purchased from Seromed. VEGF, l-glutamine, antibiotics, HEPES, DMSO, insulin, and gelatine were obtained from Sigma. Hybond ECL nitrocellulose membrane, horseradish peroxidase-linked anti-rabbit antibody, as well as ECL Western blotting detection reagents were from Amersham Life Sciences. Wortmannin and WY14643 were from Alexis Biochemicals. Fenofibrate was obtained from Sigma. Ciglitazone was purchased from Biomol. Troglitazone was
PPAR-activators inhibit endothelial cell migration
VEGF-induced migration of HUVEC was potently inhibited by all PPAR-activators tested: the PPARα-activator WY14643 led to a significant inhibition of EC-migration at 20 μmol/L (−67.2±6.5%), while fenofibrate already exerted anti-migratory actions at 10 μmol/L (−54±5.7%) and dramatically inhibited the migration response towards VEGF at 20 μmol/L (−86±4.2%, all p<0.01; Fig. 1). Even more potent effects were observed for the PPARγ-activators troglitazone and ciglitazone that inhibited EC-migration at
Discussion
The present study demonstrates that PPARα- and PPARγ-activators inhibit VEGF-induced endothelial cell migration. We also report that VEGF-induced endothelial cell migration requires activation of the PI3K → Akt and the ERK1/2 MAPK signaling pathway and that PPAR-activators exert their antimigratory effects via inhibition of the protein kinase Akt. Besides their important function in the treatment of metabolic cardiovascular risk factors, an increasing body of evidence points towards a dual
Acknowledgements
The authors would like to thank Mrs. Chantel Spencer-Hänsch for the excellent technical assistance and Mrs. Verena Fromm for her assistance in preparing the manuscript. This study was supported by the Deutsche Forschungsgemeinschaft (DFG GO 800/2-1).
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