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Updated: Mar 26, 2026
Intravital Microscopy of Leukocyte-endothelial and Platelet-leukocyte Interactions in Mesenterial Veins in Mice
Published on: August 13, 2015
Inhibitory Effect of Serotonin Antagonist on Leukocyte-Endothelial Interactions In Vivo and In Vitro
Hiroshi Kataoka1, Yuno Ariyama2, Michiyo Deushi2
1Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Insights
Sarpogrelate hydrochloride (SRPO) reduces vascular inflammation in obesity by inhibiting leukocyte-endothelial interactions. This 5-HT2A receptor inverse agonist improves obesity-related vascular issues in both animal models and cell cultures.
Area of Science:
- Pharmacology
- Vascular Biology
- Obesity Research
Background:
- 5-HT2A serotonergic antagonists are used for vascular disease in diabetes and obesity.
- Leukocyte-endothelial interactions in obesity require further investigation.
Purpose of the Study:
- To assess the effects of sarpogrelate hydrochloride (SRPO), a 5-HT2A receptor inverse agonist, on leukocyte-endothelial interactions in obesity.
- To investigate SRPO's impact on obesity-induced vascular inflammation.
Main Methods:
- In vivo: High-fat high-fructose diet (HFFD) induced obesity in mice, treated with or without SRPO. Leukocyte-endothelial interactions assessed via intravital microscopy.
- In vitro: Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were used to study cell adhesion and E-selectin expression, with or without SRPO treatment.
- Western blotting analyzed protein kinase C alpha (PKCα) activation in THP-1 cells.
Main Results:
- SRPO treatment prevented HFFD-induced increases in body weight, visceral fat, and monocyte chemoattractant protein-1 levels in mice.
- SRPO significantly reduced leukocyte-endothelial interactions in mouse femoral arteries and THP-1 cell adhesion to HUVECs.
- SRPO inhibited E-selectin upregulation in HUVECs and PKCα activation in THP-1 cells.
Conclusions:
- SRPO inhibits vascular inflammation in obesity.
- SRPO acts by inactivating platelets and leukocytes.
- SRPO demonstrates potential for improving obesity-related vascular complications.
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 α 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.
