PMID- 26824242
OWN - NLM
STAT- MEDLINE
DCOM- 20160720
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 1
DP  - 2016
TI  - Inhibitory Effect of Serotonin Antagonist on Leukocyte-Endothelial Interactions 
      In Vivo and In Vitro.
PG  - e0147929
LID - 10.1371/journal.pone.0147929 [doi]
LID - e0147929
AB  - 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. METHODS AND FINDINGS: 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 alpha activation in THP-1 cells was inhibited by SRPO. 
      CONCLUSION: Our findings indicated that SRPO inhibits vascular inflammation in 
      obesity via inactivation of platelets and leukocytes, and improvement of obese.
FAU - Kataoka, Hiroshi
AU  - Kataoka H
AD  - Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, 
      Japan.
FAU - Ariyama, Yuno
AU  - Ariyama Y
AD  - Department of Life Sciences and Bioethics, Graduate School of Medical and Dental 
      Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Deushi, Michiyo
AU  - Deushi M
AD  - Department of Life Sciences and Bioethics, Graduate School of Medical and Dental 
      Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Osaka, Mizuko
AU  - Osaka M
AD  - Department of Life Sciences and Bioethics, Graduate School of Medical and Dental 
      Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Nitta, Kosaku
AU  - Nitta K
AD  - Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, 
      Japan.
FAU - Yoshida, Masayuki
AU  - Yoshida M
AD  - Department of Life Sciences and Bioethics, Graduate School of Medical and Dental 
      Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20160129
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Serotonin 5-HT2 Receptor Antagonists)
RN  - 0 (Succinates)
RN  - 19P708E787 (sarpogrelate)
SB  - IM
MH  - Animals
MH  - Cell Adhesion/drug effects
MH  - Cell Communication/*drug effects
MH  - Cell Line
MH  - Endothelial Cells/cytology/drug effects/immunology
MH  - Endothelium, Vascular/cytology/*drug effects/immunology
MH  - Human Umbilical Vein Endothelial Cells
MH  - Inflammation/complications/drug therapy/immunology
MH  - Leukocytes/cytology/*drug effects/immunology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Obesity/*complications/*drug therapy/immunology
MH  - Serotonin 5-HT2 Receptor Antagonists/pharmacology/*therapeutic use
MH  - Succinates/pharmacology/*therapeutic use
PMC - PMC4732655
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/01/30 06:00
MHDA- 2016/07/21 06:00
PMCR- 2016/01/29
CRDT- 2016/01/30 06:00
PHST- 2015/08/09 00:00 [received]
PHST- 2016/01/11 00:00 [accepted]
PHST- 2016/01/30 06:00 [entrez]
PHST- 2016/01/30 06:00 [pubmed]
PHST- 2016/07/21 06:00 [medline]
PHST- 2016/01/29 00:00 [pmc-release]
AID - PONE-D-15-33977 [pii]
AID - 10.1371/journal.pone.0147929 [doi]
PST - epublish
SO  - PLoS One. 2016 Jan 29;11(1):e0147929. doi: 10.1371/journal.pone.0147929. 
      eCollection 2016.