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Open Access Research article

Rapamycin promoted thrombosis and platelet adhesion to endothelial cells by inducing membrane remodeling

Ping Jiang1*, Yong Lan2, Jun Luo1, Ya-Li Ren3, Dong-Ge Liu4, Jian-Xin Pang4, Jin Liu5, Jian Li1, Chen Wang6 and Jian-Ping Cai1*

Author Affiliations

1 The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, No.1, DaHua Road, Dong Dan, Beijing 100730, P.R.China

2 Department of Vascular Surgery, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China

3 Laboratory of Electron Microscopy, Peking University First Hospital, Beijing 100034, China

4 Department of Pathology, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China

5 College of Lifesciences, Beijing Normal University, Beijing 100875, China

6 Department of Respiratory Medicine, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China

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BMC Cell Biology 2014, 15:7  doi:10.1186/1471-2121-15-7

Published: 24 February 2014

Abstract

Background

Recently, evidence indicated that the rapamycin-eluting stent which was used worldwide may contribute to an increased risk for thrombosis. On the contrary, other researchers found it was safe. Thus, it is necessary to clarify the effect of rapamycin on thrombosis and the corresponding mechanisms.

Results

The effects of rapamycin in vivo were evaluated by modified deep vein thrombosis animal model. The platelets were from healthy volunteers and the platelet-endothelium (purchased from ATCC) adhesion in cultured endothelial cells was assessed. Membrane rufflings in endothelial cells were examined by confocal and electron microscope. Thrombus formation increased in rats that were injected with rapamycin. Electron microscope analysis exhibited microvilli on the rapamycin-treated endothelium in rats. Rapamycin enhanced membrane ruffling in human umbilical vein endothelial cells (HUVECs) and adhesion of platelets to HUVECs. The platelet-HUVECs adhesion was attenuated when cells were treated with cytochalacin B. Inhibition of autophagy by 3-methyladenine led to suppression of membrane ruffles in HUVECs and augmentation of platelet-endothelial adhesion.

Conclusions

In conclusion, we found that endothelial membrane remodeling induced by rapamycin is crucial for the adhesion of platelets to endothelial cells and thereby for thrombosis in vivo, and that the endothelial membrane remodeling is autophagy dependent.

Keywords:
Thrombosis; Membrane remodeling; Endothelial cell; Platelet