title: Montelukast inhibits oxidized low-density lipoproteins (ox-LDL) induced vascular endothelial attachment: An implication for the treatment of atherosclerosis.
abstract: Recruitment of monocytes to endothelial cells is important during early stages of atherosclerosis development, which is activated in response to a number of inflammatory stimuli, including oxidized low-density lipoprotein (ox-LDL). Montelukast is a licensed drug approved by the Food and Drug Administration (FDA) and clinically used for the treatment of asthma by reducing the eosinophilic inflammation in the airway. Little information regarding the effects of Montelukast on endothelial inflammation has been reported before. In the current study, we found that Montelukast markedly reduced ox-LDL-induced monocyte adhesion to human umbilical vein endothelial cells. In addition, the inhibitory mechanism of Montelukast was associated with suppression of adhesion molecule expression, including VCAM-1 and E-selectin. Mechanistically, ERK5 mediated expression of the transcriptional factor KLF2 was found to be involved in the anti-inflammation effects of Montelukast against ox-LDL induced endothelial inflammation. Results indicate that Montelukast plays a protective role in the early stages of atherosclerosis.
authors.affiliation: Department of Color Ultrasonic, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China. Electronic address: xihuadi2007@yeah.net.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Di
authors.affiliation: Department of Color Ultrasonic, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China.
authors.forename: Xuelu
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of ICU, Liaocheng Hospital of Traditional Chinese Medicine, Liaocheng 252000, China.
authors.forename: Xiuting
authors.initials: X
authors.lastname: Di
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000737:chemistry / Q000494:pharmacology; D050197:Atherosclerosis / Q000188:drug therapy / Q000517:prevention & control; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013440:Sulfides; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D019040:E-Selectin; C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D008077:Lipoproteins, LDL; D020011:Protective Agents; D011804:Quinolines; D013440:Sulfides; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D048054:Mitogen-Activated Protein Kinase 7; C093875:montelukast
keywords: Endothelial inflammation; Kruppel-like factor 2; Montelukast; Oxidized low-density lipoprotein (ox-LDL); Vascular cell adhesion molecule-1 (VCAM-1)