title: PPAR-α Agonist Fenofibrate Upregulates Tetrahydrobiopterin Level through Increasing the Expression of Guanosine 5'-Triphosphate Cyclohydrolase-I in Human Umbilical Vein Endothelial Cells.
abstract: Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide (NO) synthase. Guanosine 5'-triphosphate cyclohydrolase-I (GTPCH-I) is a key limiting enzyme for BH4 synthesis. In the present in vitro study, we investigated whether peroxisome proliferator-activated receptor α (PPAR-α) agonist fenofibrate could recouple eNOS by reversing low-expression of intracellular BH4 in endothelial cells and discussed the potential mechanisms. After human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) for 24 hours, the levels of cellular eNOS, BH4 and cell supernatant NO were significantly reduced compared to control group. And the fluorescence intensity of intracellular ROS was significantly increased. But pretreated with fenofibrate (10 umol/L) for 2 hours before cells were induced by LPS, the levels of eNOS, NO, and BH4 were significantly raised compared to LPS treatment alone. ROS production was markedly reduced in fenofibrate group than LPS group. In addition, our results showed that the level of intracellular GTPCH-I detected by western blot was increased in a concentration-dependent manner after being treated with fenofibrate. These results suggested that fenofibrate might help protect endothelial function and against atherosclerosis by increasing level of BH4 and decreasing production of ROS through upregulating the level of intracellular GTPCH-I.
authors.affiliation: Department of Endocrinology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Liu
authors.forename: Changlin
authors.initials: C
authors.lastname: Lu
authors.forename: Fuwang
authors.initials: F
authors.lastname: Li
authors.forename: Haining
authors.initials: H
authors.lastname: Wang
authors.forename: Liyun
authors.initials: L
authors.lastname: He
authors.forename: Yanting
authors.initials: Y
authors.lastname: Hao
authors.forename: Alex F
authors.initials: AF
authors.lastname: Chen
authors.forename: Huijie
authors.initials: H
authors.lastname: An
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.forename: Tianpei
authors.initials: T
authors.lastname: Hong
authors.forename: Guang
authors.initials: G
authors.lastname: Wang