title: Tetrahydroxystilbene glucoside protects against oxidized LDL-induced endothelial dysfunction via regulating vimentin cytoskeleton and its colocalization with ICAM-1 and VCAM-1.
abstract: BACKGROUND
  Endothelial cell dysfunction triggered by oxidized low-density lipoprotein (oxLDL) is the main event occurring during the development of atherosclerosis. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component of the rhizome extract from Polygonum multiflorum, exhibits significant anti-atherosclerotic activity. However, the protective effects of TSG against oxLDL-induced endothelial dysfunction have not been clarified. We investigated the cytoprotective effects of TSG in human umbilical vein endothelial cells (HUVECs) and explored underlying mechanisms.
  
  
  RESULTS
  TSG pretreatment markedly attenuated oxLDL-mediated loss of cell viability, release of lactate dehydrogenase (LDH), cell apoptosis, and monocyte adhesion. OxLDL increased vimentin mRNA and protein levels, vimentin cleavage, caspase-3 activation, adhesion molecules levels and their colocalization with vimentin in HUVECs. These alterations were attenuated by pretreatment with TSG. Meanwhile, TSG inhibited both the expression of TGFβ1 and the phosphorylation of Smad2 and Smad3, and TSG suppressed the nuclear translocation of Smad4 induced by oxLDL. Using shRNA, oxLDL-induced cell apoptosis and monocyte adhesion were significantly inhibited by vimentin suppression in HUVECs.
  
  
  CONCLUSIONS
  These results suggest that TSG protects HUVECs against oxLDL-induced endothelial dysfunction through inhibiting vimentin expression and cleavage, and the expression of adhesion molecules and their colocalization with vimentin. The interruption of TGFβ/Smad pathway and caspase-3 activation appears to be responsible for the downregulation of TSG on vimentin expression and fragmentation, respectively.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Yao
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.forename: Qinju
authors.initials: Q
authors.lastname: Sun
authors.forename: Xiang
authors.initials: X
authors.lastname: Jing
authors.forename: Huiming
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000009:adverse effects*; D016328:NF-kappa B / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051896:Smad Proteins, Receptor-Regulated / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism*
chemical_list: D005960:Glucosides; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D020011:Protective Agents; D051896:Smad Proteins, Receptor-Regulated; D013267:Stilbenes; D019010:Vascular Cell Adhesion Molecule-1; D014746:Vimentin; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D053148:Caspase 3