Dataset Information

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

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.

SUBMITTER: Jiang P

PROVIDER: S-EPMC3936831 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Jiang Ping P Lan Yong Y Luo Jun J Ren Ya-Li YL Liu Dong-Ge DG Pang Jian-Xin JX Liu Jin J Li Jian J Wang Chen C Cai Jian-Ping JP

BMC cell biology 20140224

<h4>Background</h4>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.<h4>Results</h4>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 ( ...[more]

PMID: 24564184

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Project description:BackgroundGestational diabetes mellitus (GDM) is among the most common metabolic diseases during pregnancy and inevitably leads to maternal and fetal complications. Hyperglycemia results in injury to vascular endothelial cells, including monocyte-endothelial adhesion, which is considered to be the initiating factor of vascular endothelial cell injury. Connexin 43 (Cx43) plays a key role in this adhesion process. Therefore, this study aimed to explore the effects of Cx43 on monocyte-endothelial adhesion in GDM-induced injury of vascular endothelial cells.MethodsHuman umbilical vein endothelial cells (HUVECs) were isolated from umbilical cords from pregnant women with and without GDM. THP-1 cells (a human leukemia monocytic cell line) adhering to HUVECs, related molecules [intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)], and the activity of the phosphoinositide 3-kinase/protein kinase B/Nuclear factor- kappa B (PI3K/AKT/NF-κB) signaling pathway were compared between the normal and GDM-HUVECs. Oleamide and specific small interfering ribonucleic acids (siRNAs) were used to inhibit Cx43 expression in GDM-HUVECs to observe the effects of Cx43 on the adhesion of THP-1 cells and HUVECs.ResultsA much higher number of THP-1 cells adhered to GDM-HUVECs than to normal HUVECs. This was accompanied by an increased expression of Cx43, ICAM-1, and VCAM-1, as well as activation of the PI3K/AKT/NF-κB signaling pathway. After the inhibition of Cx43 expression in GDM-HUVECs with oleamide and specific siRNA, THP-1-HUVEC adhesion, ICAM-1 and VCAM-1 expression, and activation of PI3K/AKT/NF-κB signaling pathway were all attenuated. Hyperglycemia was able to increase expression of Cx43 in HUVECs.ConclusionsFor the first time, Cx43 expression was found to be substantially higher in GDM-HUVECs than in normal HUVECs. Hyperglycemia caused the overexpression of Cx43 in HUVECs, which resulted in the activation of the PI3K/AKT/NF-κB signaling pathway and the increase of its downstream adhesion molecules, including ICAM-1 and VCAM-1, ultimately leading to increased monocyte-endothelial adhesion.

Dataset Information

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

Background

Results

Conclusions

Publications

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

Similar Datasets

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