Unknown

Dataset Information

0

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.

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 ? 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.

SUBMITTER: Kataoka H 

PROVIDER: S-EPMC4732655 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7048879 | biostudies-literature
| S-EPMC1572808 | biostudies-other
| S-EPMC4692430 | biostudies-other
| S-EPMC7237647 | biostudies-literature
| S-EPMC3819900 | biostudies-literature
| S-EPMC6335684 | biostudies-literature
| S-EPMC8740460 | biostudies-literature
| S-EPMC5733535 | biostudies-literature
| S-EPMC3359359 | biostudies-literature
| S-EPMC53544 | biostudies-other