title: Tongxinluo Regulates Expression of Tight Junction Proteins and Alleviates Endothelial Cell Monolayer Hyperpermeability via ERK-1/2 Signaling Pathway in Oxidized Low-Density Lipoprotein-Induced Human Umbilical Vein Endothelial Cells.
abstract: Vascular hyperpermeability resulting from distortion of endothelial junctions is associated with a number of cardiovascular diseases. Endothelial tight junction regulates the paracellular permeability of macromolecules, a function ofHuman Umbilical Vein Endothelial Cells(HUVEC) monolayers that can be regulated byoxidized Low-density Lipoprotein(ox-LDL). However, the understanding of drug regulation of vascular hyperpermeability is so far limited. This study thus aimed to investigate the role ofTongxinluo(TXL) in the maintenance of the vascular endothelial paracellular permeability. Here, changes in permeability were determined by measuring the paracellular flux of FITC-dextran 40000 (FD40), while protein expression and intercellular distribution were examined by western blot and immunofluorescence assay, respectively. We found that TXL alleviated the ox-LDL-induced increase in flux of FD40 and then reduced the hyperpermeability. Moreover, ox-LDL-induced disruptions of ZO-1, occludin, and claudin1 were also restored. This is via the activation of ERK1/2 in the vascular endothelial cells. Our results provide insights into the molecular mechanism by which TXL alleviates ox-LDL-induced hyperpermeability and provide the basis for further investigations of TXL as regulators of vascular barrier function.
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory of Collateral Disease Research and Innovation Medicine, Shijiazhuang 050035, China.
authors.forename: Chengcheng
authors.identifier: 0000-0002-1806-7559
authors.initials: C
authors.lastname: Chang
authors.affiliation: 2nd City Hospital, Shijiazhuang 050051, China.
authors.forename: Hongli
authors.identifier: 0000-0002-9569-8792
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Collateral Disease Research and Innovation Medicine, Shijiazhuang 050035, China; Key Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang 050035, China.
authors.forename: Cong
authors.identifier: 0000-0003-4048-6124
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang 050035, China; Graduate School, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Liping
authors.identifier: 0000-0002-8895-3337
authors.initials: L
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Collateral Disease Research and Innovation Medicine, Shijiazhuang 050035, China; Department of Pharmacology, Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang 050035, China.
authors.forename: Junqing
authors.identifier: 0000-0002-7119-2236
authors.initials: J
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Collateral Disease Research and Innovation Medicine, Shijiazhuang 050035, China; Graduate School, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Hongying
authors.identifier: 0000-0002-7810-3320
authors.initials: H
authors.lastname: Bei
authors.affiliation: Key Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang 050035, China; Graduate School, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Hongrong
authors.identifier: 0000-0003-3426-6491
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang 050035, China; Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.
authors.forename: Shen
authors.identifier: 0000-0002-7997-3061
authors.initials: S
authors.lastname: Liu
authors.affiliation: College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Key Disciplines of State Administration of TCM for Collateral Disease, Shijiazhuang 050035, China.
authors.forename: Yiling
authors.identifier: 0000-0001-9495-200X
authors.initials: Y
authors.lastname: Wu