title: Inhibitory Effect of Serotonin Antagonist on Leukocyte-Endothelial Interactions In Vivo and In Vitro.
abstract: BACKGROUND
  Although 5-HT2A serotonergic antagonists have been used to treat vascular disease in patients with diabetes mellitus or obesity, their effects on leukocyte-endothelial interactions have not been fully investigated. In this study, we assessed the effects of sarpogrelate hydrochloride (SRPO), a 5-HT2A receptor inverse agonist, on leukocyte-endothelial cell interactions in obesity both in vivo and in vitro.
  
  
  RESULTS
  In the in vivo experiment, C57BL/6 mice were fed a high-fat high-fructose diet (HFFD), comprising 20% fat and 30% fructose, with or without intraperitoneal injection of 5 mg/kg/day SRPO for 4 weeks. The body weight, visceral fat weight, and serum monocyte chemoattractant protein-1 levels in the mice increased significantly with the HFFD, but these effects were prevented by chronic injections of SRPO. Intravital microscopy of the femoral artery detected significant leukocyte-endothelial interactions after treatment with HFFD, but these leukocyte-endothelial interactions were reduced in the mice injected with SRPO. In the in vitro experiment, pre-incubation of activated human umbilical vein endothelial cells (HUVECs) with platelet-rich plasma (PRP) induced THP-1 cell adhesion under physiological flow conditions, but the adhesion was reduced by pretreatment of PRP with SRPO. A fluorescent immunobinding assay showed that PRP induced significant upregulation of E-selectin in HUVECs, but this upregulation was reduced by pretreatment of PRP with SRPO. In other in vitro conditions, pre-incubation of THP-1 cells with phorbol 12-myristate 13-acetate increased the adhesion of THP-1 cells to activated HUVECs under rotational conditions, but this adhesion was reduced by pretreatment with SRPO. Western blotting analysis showed that protein kinase C α activation in THP-1 cells was inhibited by SRPO.
  
  
  CONCLUSIONS
  Our findings indicated that SRPO inhibits vascular inflammation in obesity via inactivation of platelets and leukocytes, and improvement of obese.
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kataoka
authors.affiliation: Department of Life Sciences and Bioethics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yuno
authors.initials: Y
authors.lastname: Ariyama
authors.affiliation: Department of Life Sciences and Bioethics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Deushi
authors.affiliation: Department of Life Sciences and Bioethics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mizuko
authors.initials: M
authors.lastname: Osaka
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Nitta
authors.affiliation: Department of Life Sciences and Bioethics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D013386:Succinates / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D058830:Serotonin 5-HT2 Receptor Antagonists; D013386:Succinates; C064294:sarpogrelate
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