Pioglitazone decreased CD40/CD40L expression on human umbilical vein endothelial cells induced by oxidized low-density lipoprotein.
BACKGROUND
The CD40/CD40 ligand pathway mediated inflammatory processes are important in atherogenesis and the formation of the intraplaque lipid pool. We tested the hypothesis that pioglitazone could decrease lectin-like oxLDL receptor-1 (LOX-1) and CD40/CD40L expression on human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (oxLDL).


METHODS
HUVECs were incubated with oxLDL for 24h with or without pretreated by pioglitazone. Expression of CD40/CD40L on the cell surface was detected by flow cytometry. CD40/CD40L and LOX-1 mRNA expression were evaluated by RT-PCR. The expression of LOX-1 on HUVECs was determined by cell immunohistochemistry.


RESULTS
OxLDL increased the expression of CD40 and CD40L in a dose- and time-dependent manner. Pretreatment of HUVECs with pioglitazone (1 and 10 micromol/l) for 60 min decreased the expression of CD40 mRNA induced by oxLDL by 16% and 52%, respectively (both P<0.05). Pretreatment of HUVECs with pioglitazone (1 and 10 micromol/l) for 60 min decreased the expression of CD40L mRNA induced by oxLDL by 16% and 43% (both P<0.05). Also, pretreatment of HUVECs with pioglitazone (1 and 10 micromol/l) for 60 min also significantly decreased CD40 and CD40L expression on HUVECs induced by oxLDL in a concentration-dependent manner. Pretreatment of HUVECs with pioglitazone (1 and 10 micromol/l) decreased oxLDL induced upregulation mRNA of LOX-1 by 11% and 28%, respectively. Furthermore, through immunohistochemistry, we found that pioglitazone could decrease the LOX-1 expression on HUVECs induced by oxLDL.


CONCLUSIONS
Pioglitazone inhibited the upregulation of LOX-1 on HUVECs elicited by oxLDL and subsequently decreased HUVECs CD40/CD40L expression induced by oxLDL. These observations provided novel insight into a potential novel anti-inflammatory pathway of thiazolidinediones.
Department of Cardiology, The Second Xiangya Hospital of Central South University, Middle Ren-Min Road No. 86, ChangSha Hunan 410011, PR China. jiangdeqian@hotmail.com
De-qian
DQ
Jiang
Luo-xiang
LX
Chu
Zhao-yun
ZY
Liu
Shun-bao
SB
Zhang
D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D000077205:Pioglitazone; D051127:Scavenger Receptors, Class E / Q000235:genetics; D045162:Thiazolidinediones / Q000494:pharmacology*; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism*
D019013:CD40 Antigens; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; D045162:Thiazolidinediones; C099252:oxidized low density lipoprotein; D023201:CD40 Ligand; D000077205:Pioglitazone