title: Cariporide inhibits high glucose-mediated adhesion of monocyte-endothelial cell and expression of intercellular adhesion molecule-1.
abstract: The aim of this study was to examine whether cariporide, a new inhibitor of Na(+)/H(+) exchanger 1 (NHE-1), may inhibit high glucose-induced monocyte-endothelial cell adhesion and the expression of intercellular adhesion molecule-1 (ICAM-1). Cultured endothelial cells were incubated with normal glucose control (5.5 mM), cariporide control (5.5 mM glucose plus 10 microM cariporide), hyperosmolarity (5.5 mM glucose plus 16.5 mM mannitol), high glucose (HG, 22 mM), low-concentration cariporide (22 mM glucose plus 0.1 microM cariporide), medium-concentration cariporide (22 mM glucose plus 1 muM cariporide), and high-concentration cariporide (22 mM glucose plus 10 microM cariporide) for 24 h. Monocytes were isolated from peripheral human blood. Adhered monocytes were quantified by measuring their protein content. ICAM-1 expression and NHE-1 activity was determined with enzyme-linked immunosorbent assay (ELISA) and pH-sensitive fluorescent spectrophotometry. Exposure of endothelial cells to HG for 24 h caused an increase of adhesion of monocytes to endothelial cells and an increased expression of ICAM-1. However, these effects were reversed by treatment with cariporide (0.1, 1, 10 microM) in a concentration-dependent manner. Furthermore, cariporide (1 microM) was able to inhibit the activation of NHE-1 induced by HG in endothelial cells. These findings suggest that cariporide might inhibit HG-mediated monocyte-endothelial cell adhesion and expression of ICAM-1 by inhibiting the activation of NHE-1.
authors.affiliation: Department of Pharmacology, Pharmaceutical College, Central South University, Changsha, HN 410078, China.
authors.forename: Shuang Xi
authors.initials: SX
authors.lastname: Wang
authors.forename: Xue Ying
authors.initials: XY
authors.lastname: Sun
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Zhang
authors.forename: Shuang Xiu
authors.initials: SX
authors.lastname: Chen
authors.forename: Yu Hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Li Ying
authors.initials: LY
authors.lastname: Liu
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects*; D009994:Osmolar Concentration; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000502:physiology*; D013050:Spectrometry, Fluorescence; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D027682:Cation Transport Proteins; D006146:Guanidines; D008565:Membrane Proteins; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D018799:Intercellular Adhesion Molecule-1; C093373:cariporide; D005947:Glucose