[Time course of G-CSF, estrogen and various doses of atorvastatin on endothelial progenitor cells mobilization].
OBJECTIVE
To evaluate the time course of granulocyte-colony-stimulating-factor (G-CSF), estrogen and various doses of atorvastatin on endothelial progenitor cells (EPCs) mobilization.


METHODS
A total of 48 male New Zealand White rabbits were treated with placebo, estrogen (0.25 mg.k(-1).d(-1)), Atorvastatin (2.5, 5, or 10 mg) and G-CSF (50 microg/rabbit/d), respectively. Peripheral EPCs number was surveyed weekly for 4 weeks by FACS analysis (double-positive for PE-CD34/FITC-CD133) and under fluorescent microscope (double-positive for FITC-UEA-1/Dil-acLDL). Serum nitric oxide (NO) and lipids were also measured at the third week.


RESULTS
Peripheral EPCs was significantly increased in G-CSF treated animals and remained constant for 4 weeks compared to placebo treated animals. Atorvastatin increased peripheral EPCs dose-dependently from 2.5 to 5 mg and peaked at the third week while peripheral EPCs number was not affected by 10 mg.k(-1).d(-1) atorvastatin during the first 3 weeks and was significantly higher only in the fourth week compared to placebo group. Estrogen also significantly increased peripheral EPCs at the third and fourth week compared to placebo group. At the third week, serum NO was similar in G-CSF group, significantly higher in atorvastatin 5 mg.k(-1).d(-1) and estrogen groups while significantly lower in atorvastatin 10 mg.k(-1).d(-1) group compared to placebo group. Serum lipids were similar among various groups.


CONCLUSIONS
Atorvastatin, estrogen and G-CSF could mobilize EPCs. The mobilization efficacy is as follows: G-CSF > atorvastatin 5 mg.k(-1).d(-1) > estrogen > atorvastatin 2.5 mg.k(-1).d(-1) > atorvastatin 10 mg.k(-1).d(-1). NO might partly contribute to the mobilizing effect of estrogen and atorvastatin.
Xiao
Chuan-shi
CS
Department of Cardiology, Second Hospital of Shan Xi Medical University, Taiyuan 030001, China.
Wang
Gai-ling
GL
Zhao
Wen-yan
WY
Qiu
Ling
L
Li
Mao-lian
ML
Zeng
Qiu-tang
QT
D000818:Animals; D000069059:Atorvastatin; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004967:Estrogens / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008055:Lipids / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins; D013234:Stem Cells / Q000187:drug effects*
D004967:Estrogens; D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; D008055:Lipids; D011758:Pyrroles; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D009569:Nitric Oxide; D000069059:Atorvastatin