Aim: The aim of the study was to
investigate whether lovastatin restores the survival and function of
endothelial progenitor cells (EPCs) damaged by oxLDL.
Methods: EPCs were preincubated with
different concentrations of lovastatin (2, 10, and 50 µmol/L) with or without
the Akt inhibitor triciribine for 24 h and were then exposed to 50 µg/mL oxLDL
for 48 h. The survival of EPCs, as well as the cellular migration, adhesion,
and tube formation of these cells, was examined. To explore the mechanisms of
lovastatin’s effects on EPCs, the levels of phosphorylated Akt and eNOS and of
total eNOS protein and mRNA were assayed.
Results: Incubation of EPCs with oxLDL
resulted in significant apoptosis and impaired cellular migration, adhesion and
tube structure formation. The detrimental effects of oxLDL on EPC survival and
function were attenuated by pretreatment of EPCs with lovastatin. However, when EPCs were pretreated with
lovastatin and triciribine at the same time, the beneficial effects of
lovastatin were abolished by triciribine. Furthermore, oxLDL caused a significant downregulation of eNOS mRNA and
protein expression, as well as a suppression of Akt and eNOS
phosphorylation. However, the
effects of oxLDL on Akt/eNOS activity and eNOS expression were reversed by
lovastatin.
Conclusion: Lovastatin reverses the
survival and function of EPCs by regulating the Akt/eNOS signaling pathway and
the gene transcription of eNOS. |
