[In vitro study of the effects of pioglitazone on endothelial cell functions of human umbilical vein and the mechanisms involved].
OBJECTIVE
To determine whether pioglitazone (PIO) has effects on human umbilical vein endothelial cells (HUVECs) in vitro and to clarify the possible mechanisms therein involved.


METHODS
The HUVECs were selected to be a model, which was cultured with 5.5 mmol/L glucose (control group), 30 mmol/L glucose (high glucose group), and 30 mmol/L glucose+PIO at 10(-9), 10(-7), 10(-5) mol/L respectively (PIO+high glucose groups). The effects of the drugs on the endothelial dysfunction induced by high glucose were studied. The role of protein kinase C (PKC) alpha and delta in the endothelial dysfunction induced by high glucose and the effects of PIO were assessed. The translocation of PKCdelta or PKCalpha in a single HUVEC was observed by Laser-Scanning Confocal Microscope, and the expression analysis was conducted quantificationally by Western blotting.


RESULTS
High glucose could induce HUVECs apoptosis; the concentration of NO reduced and the level of sICAM-1 increased in high glucose group. PIO could inhibit the increasing apoptosis peaks induced by high glucose and could reverse the concentration of NO and sICAM-1 to normal level. PIO could inhibit the translocation of PKCa from plasm to nucleus in HUVECs induced by high glucose; it also could inhibit the translocation of PKCdelta from nucleus to plasm and membrane in HUVECs. PIO could inhibit the increasing expression of PKCdelta in HUVECs induced by high glucose. The expression level of PKCalpha in the high glucose group was not significantly different from that in the control.


CONCLUSIONS
PIO could correct the endothelial cell dysfunction induced by high glucose, and this drug action of PIO may be effected via the inhibition of PKCalpha and PKCdelta.
Tong
Nan-wei
NW
Department of Endocrinology, West China Hospital, Sichuan University, Chengdu 610041, China.
Wan
Qin
Q
Liu
Xiao-jing
XJ
Wu
Hui
H
D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D009569:Nitric Oxide / Q000378:metabolism; D000077205:Pioglitazone; D011493:Protein Kinase C / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D009569:Nitric Oxide; D011493:Protein Kinase C; D005947:Glucose; D000077205:Pioglitazone