Jiang De-qian, Chu Luo-xiang, Liu Zhao-yun, Zhang Shun-bao
Department of Cardiology, The Second Xiangya Hospital of Central South University, Middle Ren-Min Road No. 86, ChangSha Hunan 410011, PR China.
Clin Chim Acta. 2006 Aug;370(1-2):94-9. doi: 10.1016/j.cca.2006.01.026. Epub 2006 Mar 20.
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).
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.
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.
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.
CD40/CD40配体途径介导的炎症过程在动脉粥样硬化形成及斑块内脂质池形成中起重要作用。我们检验了吡格列酮可降低氧化型低密度脂蛋白（oxLDL）诱导的人脐静脉内皮细胞（HUVECs）上凝集素样氧化型低密度脂蛋白受体-1（LOX-1）及CD40/CD40L表达的假说。
将HUVECs与oxLDL孵育24小时，吡格列酮预处理或不预处理。通过流式细胞术检测细胞表面CD40/CD40L的表达。通过逆转录聚合酶链反应（RT-PCR）评估CD40/CD40L及LOX-1 mRNA的表达。通过细胞免疫组织化学测定HUVECs上LOX-1的表达。
oxLDL以剂量和时间依赖性方式增加CD40和CD40L的表达。用吡格列酮（1和10微摩尔/升）预处理HUVECs 60分钟，分别使oxLDL诱导的CD40 mRNA表达降低16%和52%（均P<0.05）。用吡格列酮（1和10微摩尔/升）预处理HUVECs 60分钟，使oxLDL诱导的CD40L mRNA表达降低16%和43%（均P<0.05）。此外，用吡格列酮（1和10微摩尔/升）预处理HUVECs 60分钟也以浓度依赖性方式显著降低oxLDL诱导的HUVECs上CD40和CD40L的表达。用吡格列酮（1和10微摩尔/升）预处理HUVECs分别使oxLDL诱导的LOX-1上调mRNA降低11%和28%。此外，通过免疫组织化学，我们发现吡格列酮可降低oxLDL诱导的HUVECs上LOX-1的表达。
吡格列酮抑制oxLDL引起的HUVECs上LOX-1的上调，随后降低oxLDL诱导的HUVECs CD40/CD40L表达。这些观察结果为噻唑烷二酮类潜在的新型抗炎途径提供了新见解。
