Lovastatin restores the function of endothelial progenitor cells damaged by oxLDL.
OBJECTIVE
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 micromol/L) with or without the Akt inhibitor triciribine for 24 h and were then exposed to 50 microg/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.


CONCLUSIONS
Lovastatin reverses the survival and function of EPCs by regulating the Akt/eNOS signaling pathway and the gene transcription of eNOS.
State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin 300020, China.
Feng-xia
FX
Ma
Fang
F
Chen
Qian
Q
Ren
Zhong-chao
ZC
Han
D018952:Antigens, CD34 / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000009:adverse effects*; D008148:Lovastatin / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D018952:Antigens, CD34; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008148:Lovastatin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt