title: The inhibitory effect of alacepril, an angiotensin-converting enzyme inhibitor, on endothelial inflammatory response induced by oxysterol and TNF-alpha.
abstract: The objectives were to determine the effects of alacepril, an angiotensin-converting enzyme inhibitor, on the expression of adhesion molecules and monocyte adherence to endothelial cells induced by 7-ketocholesterol (7-KC) and tumor necrosis factor (TNF)-alpha. We used human aortic endothelial cells (HAECs) and U937 monocytic cells. Surface expression and mRNA levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were determined by EIA and RT-PCR. Adherence of U937 to HAECs was assessed by adhesion assay. Incubation of HAEC with 7-KC increased the surface expression of protein and mRNA levels of ICAM-1 and VCAM-1 on HAECs and the production of reactive oxygen species (ROS) in HAECs. Pretreatment with alacepril reduced the enhanced expression of these molecules in a dose-dependent manner. The inhibitory effect of alacepril against 7-KC or TNF-alpha-induced CAMs expression was stronger than that of captopril or enalapril. Alacepril inhibited the production of ROS in HAECs stimulated by 7-KC or TNF-alpha. These results suggest that alacepril works as anti-atherogenic agent through inhibiting endothelial-dependent adhesive interactions with monocytes induced by 7-KC and TNF-alpha.
authors.affiliation: Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimozawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Hiroki
authors.initials: H
authors.lastname: Manabe
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katada
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kuroda
authors.forename: Nami
authors.initials: N
authors.lastname: Nakabe
authors.forename: Norimasa
authors.initials: N
authors.lastname: Yoshida
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007653:Ketocholesterols / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007653:Ketocholesterols; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004656:Enalapril; C048162:desacetyl-alacepril; D002216:Captopril; C003001:7-ketocholesterol; C046835:alacepril