title: Effect of rosuvastatin on OX40L and PPAR-γ expression in human umbilical vein endothelial cells and atherosclerotic cerebral infarction patients.
abstract: Atherosclerotic cerebral infarction (ACI) is characterized by extremely high fatality and disability rate. Recent studies indicate that co-stimulatory signal of tumor necrosis factor superfamily OX40/OX40L contributes to the atherosclerosis effect in ACI patients. However, it remains unclear the mechanism underlying the anti-atherosclerosis process. So this study aims to investigate the effects of rosuvastatin on the expression of OX40L, peroxisome proliferator-activated receptors gamma (PPAR-γ) in human umbilical vein endothelial cells (HUVEC), and human peripheral blood lymphocytes. Different concentration of rosuvastatin and oxidized low-density lipoprotein (OX-LDL) co-intervene HUVEC to observe the expression of OX40L and PPAR-γ using real-time quantitative RT-PCR (Q-RTPCR) and Western-blot. Furthermore, we examined the level changes of plasmic sOX40L and hs-CRP in acute atherosclerotic cerebral infarction patients. The results demonstrated that concentration-dependent and time-dependent OX-LDL remarkably stimulate the expression of OX40L and inhibit the expression of PPAR-γ in vitro. But concentration-dependent rosuvastatin can reverse the impact of OX-LDL, suggesting that rosuvastatin can prevent the expression of OX40L, and the process may be associated with mevalonate pathway. In vivo, acute atherosclerotic cerebral infarction patients taking 20 mg rosuvastatin exhibited significantly reduced expression of OX40L in peripheral blood lymphocyte, sOX40L in blood plasma, and hs-CRP compared with before treatment. Our studies identified rosuvastatin as an effective medicine in controlling atherosclerosis process in ACI by inhibiting OX40L and stimulating PPAR-γ expression.
authors.affiliation: Department of Neurology, The fourth affiliated hospital of Harbin Medical University, Yiyuan Street 37, Harbin, Heilongjiang Province, People's Republic of China, 7150001.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Wang
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Zhang
authors.forename: Feng-Jun
authors.initials: FJ
authors.lastname: Wang
mesh_terms: D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology* / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002537:Intracranial Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D053278:OX40 Ligand / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053278:OX40 Ligand; D047495:PPAR gamma; D011743:Pyrimidines; D013449:Sulfonamides; C089251:TNFSF4 protein, human; D000068718:Rosuvastatin Calcium