Abstract
BackgroundAlthough 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 FindingsIn 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.ConclusionOur findings indicated that SRPO inhibits vascular inflammation in obesity via inactivation of platelets and leukocytes, and improvement of obese.
Highlights
Serotonin/5-hydroxytryptamine (5-HT) and its receptor 5-HT2AR, a member of the G protein —coupled receptor (GPCR) family, are known to have effects on atherosclerosis-associated conditions, including body weight [1], abdominal fat weight [2], and glucose and lipid metabolism [3]
Our findings indicated that Sarpogrelate hydrochloride (SRPO) inhibits vascular inflammation in obesity via inactivation of platelets and leukocytes, and improvement of obese
The body weight, epididymal fat weight, and liver weight were significantly higher in the HFFD with VEH group than those in the normal chow (NC) group, which was blunted in the HFFD with SRPO treatment
Summary
Serotonin/5-hydroxytryptamine (5-HT) and its receptor 5-HT2AR, a member of the G protein —coupled receptor (GPCR) family, are known to have effects on atherosclerosis-associated conditions, including body weight [1], abdominal fat weight [2], and glucose and lipid metabolism [3]. The 5-HT-dependent pathway plays a role in inflammatory cytokine production [5, 9], leukocyte activation [10], and platelet activation [11]. Sarpogrelate hydrochloride (SRPO), an anti-platelet drug that has been used to prevent thrombosis in atherosclerotic diseases, is a 5-HT2A receptor antagonist. We assessed the anti-inflammatory effects of SRPO on leukocyte-endothelial cell interactions both in vitro and in vivo. 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. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
