Activation of peroxisome proliferator-activated receptor alpha in human endothelial cells increases plasminogen activator inhibitor type-1 expression.
OBJECTIVE
To investigate the effect of peroxisome proliferator-activated receptors (PPARs) activators on plasminogen activator inhibitor 1 (PAI-1) expression in human umbilical vein endothelial cells and elucidate a possible mechanism.


METHODS
Human umbilical vein endothelial cells (HUVECs) were obtained from normal fetus, and cultured conventionally. Then the HUVEC were exposed to fatty acids and prostaglandin J(2) in varying concentrations with fresh media. RT-PCR and ELISA were used to determine the expression of PPAR and PAI-1 in HUVECs. Transient co-transfection of PAI-1 promoter and PPARalpha gene or PPARgamma gene to ECV304 was performed.


RESULTS
PPARalpha, PPARdelta and PPARgamma mRNA in HUVECs were detected by RT-PCR. Treatment of HUVECs with PPARalpha and PPARgamma activators-linolenic acid, linoleic acid, oleic acid and prostaglandin J(2), but not with stearic acid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner. Proportional induction of PAI-1 promoter activity was observed through increasing amounts of PPARalpha DNA in HUVECs through a transient gene transfection assay, although the mRNA expression of the 3 subtypes of PPAR with their activators were not changed compared with controls.


CONCLUSIONS
HUVECs express PPARs. PPARs activators may increase PAI-1 expression in endothelial cells (EC). Although PPARs expression was not enhanced after being stimulated by their activators in EC, the functionally active PPARalpha is probably involved in regulating PAI-1 expression in EC.
Ye
Ping
P
Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China. yeping@midwest.com.cn
Hu
Xiaohui
X
Liu
Yongxue
Y
Zhao
Yali
Y
D002478:Cells, Cultured; D005227:Fatty Acids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D005227:Fatty Acids; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2