title: Trichosanatine alleviates oxidized low-density lipoprotein induced endothelial cells injury via inhibiting the LOX-1/p38 MAPK pathway.
abstract: The LOX-1/p38 mitogen-activated protein kinase (MAPK) pathway has been proved to participate in the endothelial dysfunction in atherosclerosis. Trichosanatineis is an active compound isolated from the peel ofTrichosanthes kirilowii. This study aims to determine whether trichosanatine prevents the oxidized low-density lipoprotein (ox-LDL)-induced insult through inhibition of the LOX-1/p38 MAPK pathway in HUVECs. HUVECs were treated with 150 mg/ml ox-LDL for 24 h to establish an ox-LDL-induced endothelial injury model. Cell viability, mitochondrial membrane potential (MMP), apoptosis, reactive oxygen species (ROS) level, LOX-1 and p38 MAPK expression level were measured. The results indicated that HUVECs were pretreated with either 100 mM trichosanatine or LOX-1 shRNA prior to exposure to ox-LDL for 24 h. Exposure of HUVECs to 150 mg/ml ox-LDL for 24 h significantly up-regulated the expression levels of LOX-1. The increased expression levels of LOX-1 were markedly attenuated by pretreatment with 100 mM trichosanatine. In addition, the ox-LDL-induced increase in phosphorylated (p) p38 MAPK expression was ameliorated by pretreatment with LOX-1 shRNA. Pretreatment of HUVECs with either trichosanatine or LOX-1 shRNA before exposure to ox-LDL significantly inhibited the ox-LDL-induced injuries, as evidenced by an increase in cell viability, a decrease in apoptotic cells, a ROS generation and a loss of MMP. In conclusion, we have demonstrated for the first time that the LOX-1/p38 MAPK pathway contributes to the ox-LDL-induced injury in HUVECs. Meanwhile, the trichosanatine protects the HUVECs against ox-LDL-induced injury at least in part by inhibiting the activated of LOX-1/p38 MAPK pathway.
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, P. R. China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Jia
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, P. R. China.
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Zhao
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, P. R. China.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Zhou
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, P. R. China.
authors.forename: Yun-Yun
authors.initials: YY
authors.lastname: Pan
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, P. R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wan
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, P. R. China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Cui
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, P. R. China.
authors.forename: Xue-Gang
authors.initials: XG
authors.lastname: Sun
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, P. R. China.
authors.forename: Yu-Yao
authors.initials: YY
authors.lastname: Chen
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, P. R. China.
authors.forename: Sai-Bo
authors.initials: SB
authors.lastname: Cheng
keywords: LOX-1; Trichosanatine; oxidized low-density lipoprotein; p38 mitogen-activated protein kinase